Novel human proteins, polynucleotides encoding them and methods of using the same

ABSTRACT

Disclosed herein are nucleic acid sequences that encode novel polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies that immunospecifically bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the novel polypeptide, polynucleotide, or antibody specific to the polypeptide. Vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using same are also included. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

RELATED APPLICATIONS

[0001] This application claims priority to provisional patentapplication serial Nos. 60/309501, filed on Aug. 2, 2001; 60/310291,filed on Aug. 3, 2001; 60/361775, filed on Mar. 5, 2002; 60/310951,filed on Aug. 8, 2001; 60/361832, filed on Mar. 5, 2002; 60/311292,filed on Aug. 9, 2001; 60/311979, filed on Aug. 13, 2001; 60/312203,filed on Aug. 14, 2001; 60/313201, filed on Aug. 17, 2001; 60/313702,filed on Aug. 20, 2001; 60/313643, filed on Aug. 20, 2001; 60/314031,filed on Aug. 21, 2001; 60/314466, filed on Aug. 23, 2001; 60/315403,filed on Aug. 28, 2001; and 60/315853, filed on Aug. 29, 2001, each ofwhich is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to nucleic acids encoding proteinsthat are new members of the following protein families: MAP kinasephosphatase-like proteins, cyclin-like proteins, GAG-like proteins,RasGEF domain containing proteins, novel Guanine-nucleotide exchangefactor-like proteins, MAXP1-like proteins, Retinoblastoma bindingprotein p48-like proteins, XAF-1-like proteins (with zinc fingermotifs), novel XIAP-associated Factor 1-like proteins, profilin-likeproteins, syntenin-2BETA-like proteins, PLK Interacting protein-likeproteins, intercellular protein-like proteins, Adenosine-deaminase(editase)-like proteins, Leiomodin-like proteins, Faciogenital dysplasiaFactor 3-like proteins, collybistin 1-like proteins, splice variant ofN-terminal kinase-like (NTKL)-like proteins, neurobeachin-like proteins,leucine-rich repeat protein-like proteins, synaptotagmin-like proteins,granuphilin A-like proteins, nuclear dual-specificity phsophatase-likeproteins, zinc finger (C2H2) domain-like proteins, NADH-UbiquinoneOxidoreductase 13 KDA-B subunit-like proteins, 1700003M02RIKprotein-like proteins, Negative Regulator Of Translation-like proteins,4E-Binding, Protein 2-like proteins, hypothetical intracellularproteins, CAP-Gly domain-containing proteins, Differentiation EnhancingFactor 1-like proteins, C2-domain containing, proteins,Oxystyrol-binding protein homolog 1-like proteins, Channel interactingPDZ domain-like proteins, and Similar to SRC homology (SH3) andCysteine-rich Domain protein-like proteins.

[0003] Included in the invention are polynucleotides and thepolypeptides encoded by such polynucleotides, as well as vectors, hostcells, antibodies and recombinant methods for producing the polypeptidesand polynucleotides, as well as methods for using the same. Methods ofuse encompass diagnostic and prognostic assay procedures as well asmethods of treating diverse pathological conditions.

BACKGROUND OF THE INVENTION

[0004] The invention generally relates to nucleic acids and polypeptidesencoded therefrom. More specifically, the invention relates to nucleicacids encoding cytoplasmic, nuclear, membrane bound, and secretedpolypeptides, as well as vectors, host cells, antibodies, andrecombinant methods for producing these nucleic acids and polypeptides.

SUMMARY OF THE INVENTION

[0005] The present invention is based in part on nucleic acids encodingproteins that are members of the following protein families: MAP kinasephosphatase-like proteins, cyclin-like proteins, GAG-like proteins,RasGEF domain containing proteins, novel Guanine-nucleotide exchangefactor-like proteins, MAXP1-like proteins, Retinoblastoma bindingprotein p48-like proteins, XAF-1 Zinc finger-like proteins, novelXIAP-associated Factor l-like proteins, profilin-like proteins,syntenin-2BETA-like proteins, PLK Interacting protein-like proteins,intracellular protein-like proteins, Adenosine-deaminase (editase)-likeproteins, Leiomodin-like proteins, Faciogenital dysplasia Factor 3-likeproteins, collybistin 1-like proteins, splice variant of N-terminalkinase-like (NTKL)-like proteins, neurobeachin-like proteins,leucine-rich repeat protein-like proteins, synaptotagmin-like proteins,granuphilin A-like proteins, nuclear dual-specificity phsophatase-likeproteins, zinc finger (C2H2) domain-like proteins, NADH-UbiquinoneOxidoreductase 13 KDA-B subunit-like proteins, 1700003M02RIKprotein-like proteins, Negative Regulator Of Translation-like proteins,4E-Binding Protein 2-like proteins, hypothetical intracellular proteins,CAP-Gly domain-containing proteins, Differentiation Enhancing Factor1-like proteins, C2-domain containing proteins, Oxystyrol-bindingprotein homolog 1-like proteins, Channel interacting PDZ domain-likeproteins, and Similar to SRC homology (SH3) and Cysteine-rich Domainprotein-like proteins. The novel polynucleotides and polypeptides arereferred to herein as NOV1a, NOV2a, NOV2b, NOV3a, NOV4a, NOV4b, NOV5a,NOV6a, NOV7a, NOV7b, NOV8a, NOV8b, NOV9a, NOV10a, NOV10b, NOV11a,NOV12a, NOV13a, NOV14a, NOV15a, NOV16a, NOV17a, NOV18a, NOV18b, NOV19a,NOV20a, NOV21a, NOV22a, NOV23a, NOV24a, NOV25a, NOV26a, NOV27a, NOV28a,NOV29a, NOV30a, NOV31a, NOV32a, NOV33a, NOV34a, NOV35a, NOV35b, NOV36a,NOV36b. These nucleic acids and polypeptides, as well as derivatives,homologs, analogs and fragments thereof, will hereinafter becollectively designated as “NOVX” nucleic acid or polypeptide sequences.

[0006] In one aspect, the invention provides an isolated NOVX nucleicacid disclosed in SEQ ID NO:2n-1, wherein n is an integer between 1 and44. In some embodiments, the NOVX nucleic acid molecule will hybridizeunder stringent conditions to a nucleic acid sequence complementary to anucleic acid molecule that includes a protein-coding sequence of a NOVXnucleic acid sequence. The invention also includes an isolated nucleicacid that encodes a NOVX polypeptide, or a fragment, homolog, analog orderivative thereof. For example, the nucleic acid can encode apolypeptide at least 80% identical to a polypeptide comprising the aminoacid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and44. The nucleic acid can be, for example, a genomic DNA fragment or acDNA molecule that includes the nucleic acid sequence of any of SEQ IDNO:2n-1, wherein n is an integer between 1 and 44. Also included in theinvention is an oligonucleotide, e.g. an oligonucleotide which includesat least 6 contiguous nucleotides of a NOVX nucleic acid (e.g., SEQ IDNO:2n-1, wherein n is an integer between 1 and 44) or a complement ofsaid oligonucleotide.

[0007] The invention also encompasses isolated NOVX polypeptides (SEQ IDNO:2n, wherein n is an integer between 1 and 44). In certainembodiments, the NOVX polypeptides include an amino acid sequence thatis substantially identical to the amino acid sequence of a human NOVXpolypeptide.

[0008] The invention also features antibodies that immunoselectivelybind to NOVX polypeptides, or fragments, homologs, analogs orderivatives thereof.

[0009] In another aspect, the invention includes pharmaceuticalcompositions that include therapeutically- or prophylactically-effectiveamounts of a therapeutic and a pharmaceutically-acceptable carrier. Thetherapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or anantibody specific for a NOVX polypeptide. In a further aspect, theinvention includes, in one or more containers, a therapeutically- orprophylactically-effective amount of this pharmaceutical composition.

[0010] In a further aspect, the invention includes a method of producinga polypeptide by culturing a cell that includes a NOVX nucleic acid,under conditions allowing for expression of the NOVX polypeptide encodedby the DNA. If desired, the NOVX polypeptide can then be recovered.

[0011] In another aspect, the invention includes a method of detectingthe presence of a NOVX polypeptide in a sample. In the method, a sampleis contacted with a compound that selectively binds to the polypeptideunder conditions allowing for formation of a complex between thepolypeptide and the compound. The complex is detected, if present,thereby identifying the NOVX polypeptide within the sample.

[0012] The invention also includes methods to identify specific cell ortissue types based on their expression of a NOVX.

[0013] Also included in the invention is a method of detecting thepresence of a NOVX nucleic acid molecule in a sample by contacting thesample with a NOVX nucleic acid probe or primer, and detecting whetherthe nucleic acid probe or primer bound to a NOVX nucleic acid moleculein the sample.

[0014] In a further aspect, the invention provides a method formodulating the activity of a NOVX polypeptide by contacting a cellsample that includes the NOVX polypeptide with a compound that binds tothe NOVX polypeptide in an amount sufficient to modulate the activity ofsaid polypeptide. The compound can be, e.g., a small molecule, such as anucleic acid, peptide, polypeptide, peptidomimetic, carbohydrate, lipidor other organic (carbon containing) or inorganic molecule, as furtherdescribed herein.

[0015] In another embodiment, the invention involves a method foridentifying a potential therapeutic agent for use in treatment of apathology, herein the pathology is related to aberrant expression oraberrant physiological interactions of a polypeptide with an amino acidsequence selected from the group consisting of SEQ ID NO:2n, wherein nis an integer between 1 and 44, the method including providing a cellexpressing the polypeptide of the invention and having a property orfunction ascribable to the polypeptide; contacting the cell with acomposition comprising a candidate substance; and determining whetherthe substance alters the property or function ascribable to thepolypeptide; whereby, if an alteration observed in the presence of thesubstance is not observed when the cell is contacted with a compositiondevoid of the substance, the substance is identified as a potentialtherapeutic agent.

[0016] Also within the scope of the invention is the use of atherapeutic in the manufacture of a medicament for treating orpreventing disorders or syndromes including, e.g., adrenoleukodystrophy,congenital adrenal hyperplasia, hemophilia, hypercoagulation, idiopathicthrombocytopenic purpura, autoimmune disease, allergies,immunodeficiencies, Von Hippel-Lindau (VHL) syndrome, Alzheimer'sdisease, stroke, tuberous sclerosis, hypercalcemia, Parkinson's disease,Huntington's disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome,multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioraldisorders, addiction, anxiety, pain, diabetes, renal artery stenosis,interstitial nephritis, glomerulonephritis, polycystic kidney disease,systemic lupus erythematosus renal tubular acidosis, IgA nephropathy,asthma, emphysema, scleroderma, adult respiratory distress syndrome(ARDS), lymphedema, graft versus host disease (GVHD), pancreatitis,obesity, ulcers, anemia, ataxia-telangiectasia, cancer, trauma, viralinfections, bacterial infections, parasitic infections; and conditionsrelated to transplantation, neuroprotection, fertility, or regeneration(in vitro and in vivo), faciogenital dysplasia and/or other pathologiesand disorders of the like. Also within the scope of the invention is theuse of a therapeutic in the manufacture of a medicament for treating orpreventing conditions including, e.g., those associated with homologs ofa NOVX sequence, such as those listed in Table A.

[0017] The therapeutic can be, e.g., a NOVX nucleic acid, a NOVXpolypeptide, or a NOVX-specific antibody, or biologically-activederivatives or fragments thereof.

[0018] For example, the compositions of the present invention will haveefficacy for treatment of patients suffering from the diseases anddisorders disclosed above and/or other pathologies and disorders of thelike. The polypeptides can be used as immunogens to produce antibodiesspecific for the invention, and as vaccines. They can also be used toscreen for potential agonist and antagonist Compounds. For example, acDNA encoding NOVX may be useful in gene therapy, and NOVX may be usefulwhen administered to a subject in need thereof.

[0019] The invention further includes a method for screening for amodulator of disorders or syndromes including, e.g., the diseases anddisorders disclosed above and/or other pathologies and disorders of thelike. The method includes contacting a test compound with a NOVXpolypeptide and determining if the test compound binds to said NOVXpolypeptide. Binding of the test compound to the NOVX polypeptideindicates the test compound is a modulator of activity, or of latency orpredisposition to the aforementioned disorders or syndromes.

[0020] Also within the scope of the invention is a method for screeningfor a modulator of activity, or of latency or predisposition todisorders or syndromes including, e.g., the diseases and disordersdisclosed above and/or other pathologies and disorders of the like byadministering a test compound to a test animal at increased risk for theaforementioned disorders or syndromes. The test animal expresses arecombinant polypeptide encoded by a NOVX nucleic acid. Expression oractivity of NOVX polypeptide is then measured in the test animal, as isexpression or activity of the protein in a control animal whichrecombinantly-expresses NOVX polypeptide and is not at increased riskfor the disorder or syndrome. Next, the expression of NOVX polypeptidein both the test animal and the control animal is compared. A change inthe activity of NOVX polypeptide in the test animal relative to thecontrol animal indicates the test compound is a modulator of latency ofthe disorder or syndrome.

[0021] In yet another aspect, the invention includes a method fordetermining the presence of or predisposition to a disease associatedwith altered levels of a NOVX polypeptide, a NOVX nucleic acid, or both,in a subject (e.g., a human subject). The method includes measuring theamount of the NOVX polypeptide in a test sample from the subject andcomparing the amount of the polypeptide in the test sample to the amountof the NOVX polypeptide present in a control sample. An alteration inthe level of the NOVX polypeptide in the test sample as compared to thecontrol sample indicates the presence of or predisposition to a diseasein the subject. Preferably, the predisposition includes, e.g., thediseases and disorders disclosed above and/or other pathologies anddisorders of the like. Also, the expression levels of the newpolypeptides of the invention can be used in a method to screen forvarious cancers as well as to determine the stage of cancers.

[0022] In a further aspect, the invention includes a method of treatingor preventing a pathological condition associated with a disorder in amammal by administering to the subject a NOVX polypeptide, a NOVXnucleic acid, or a NOVX-specific antibody to a subject (e.g., a humansubject), in an amount sufficient to alleviate or prevent thepathological condition. In preferred embodiments, the disorder,includes, e.g., the diseases and disorders disclosed above and/or otherpathologies and disorders of the like.

[0023] In yet another aspect, the invention can be used in a method toidentity the cellular receptors and downstream effectors of theinvention by any one of a number of techniques commonly employed in theart. These include but are not limited to the two-hybrid system,affinity purification, co-precipitation with antibodies or otherspecific-interacting molecules.

[0024] NOVX nucleic acids and polypeptides are further useful in thegeneration of antibodies that bind immuno-specifically to the novel NOVXsubstances for use in therapeutic or diagnostic methods. These NOVXantibodies may be generated according to methods known in the art, usingprediction from hydrophobicity charts, as described in the “Anti-NOVXAntibodies” section below. The disclosed NOVX proteins have multiplehydrophilic regions, each of which can be used as an immunogen. TheseNOVX proteins can be used in assay systems for functional analysis ofvarious human disorders, which will help in understanding of pathologyof the disease and development of new drug targets for variousdisorders.

[0025] The NOVX nucleic acids and proteins identified here may be usefulin potential therapeutic applications implicated in (but not limited to)various pathologies and disorders as indicated below. The potentialtherapeutic applications for this invention include, but are not limitedto: protein therapeutic, small molecule drug target, antibody target(therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnosticand/or prognostic marker, gene therapy (gene delivery/gene ablation),research tools, tissue regeneration in vivo and in vitro of all tissuesand cell types composing (but not limited to) those defined here.

[0026] Unless otherwise defined, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this invention belongs Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present invention, suitable methods andmaterials are described below. All publications, patent applications,patents, and other references mentioned herein are incorporated byreference in their entirety. In the case of conflict, the presentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

[0027] Other features and advantages of the invention will be apparentfrom the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0028] The present invention provides novel nucleotides and polypeptidesencoded thereby. Included in the invention are the novel nucleic acidsequences, their encoded polypeptides, antibodies, and other relatedcompounds. The sequences are collectively referred to herein as “NOVXnucleic acids” or “NOVX polynucleotides” and the corresponding encodedpolypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.”Unless indicated otherwise, “NOVX” is meant to refer to any of the novelsequences disclosed herein. Table A provides a summary of the NOVXnucleic acids and their encoded polypeptides. TABLE A Sequences andCorresponding SEQ ID Numbers SEQ ID SEQ NO ID NO NOVX Internal (nucleic(amino Assignment Identification acid) acid) Homology  1a CC102071-01 12 MAP kinase phosphatase-like  2a CG112767-01 3 4 Cyclin-like  2bCG112767-02 5 6 Cyclin-like  3a CG112776-01 7 8 Gag-like  4a CG122759-019 10 RasGEF domain containing protein-like  4b CG122759-02 11 12 NovelGuanine nucleotide exchange factor-like  5a CG124599-01 13 14 MAXP1-like 6a CG125142-01 15 16 Retinoblastoma Binding Protein P48-like  7aCG125414-01 17 18 XAF-1 zinc finger motif-like  7b CG125414-02 19 20Novel XIAP Associated Factor 1-like  8a CG127770-01 21 22 Profilin1-like  8b CG127770-02 23 24 Profilin 1-like  9a CG127897-01 25 26Syntenin 2BETA-like 10a CG127936-01 27 28 PLK interacting protein-like10b CG127936-02 29 30 PLK interacting protein-like 11a CG127954-01 31 32Intracellular protein-like 12a CC128132-01 33 34 RAL-A Exchange FactorRALCPS2-like 13a CGl28219-01 35 36 Adenosine-deaminase (editase)-like14a CG128389-01 37 38 Leiomodin-like 15a CG128613-01 39 40 Faciogenitaldysplasia protein 3-like 16a CG128685-01 41 42 Collybistin 1-like 17aCG128937-01 43 44 splice variant of N-terminal kinase-like (NTKL) like18a CG132095-01 45 46 Intracellular protein-like 18b CG132095-02 47 48Intracellular protein-like 19a CG132414-01 49 50 Neurobeachin-like 20aCG133140-01 51 52 Leucine-rich repeat protein-like 21a CG133369-01 53 54Synaptotagmin-like 22a CG133456-01 55 56 Granuphilin-A-like 23aCG133903-01 57 58 Nuclear dual-specificity phosphatase-like 24aCG133995-01 59 60 Zinc finger (C2H2) domain like 25a CC134005-01 61 62NADH-Ubiquinone Oxidoreductase 13 KDA-B Subunit like 26a CG134014-01 6364 1700003M02R1K Protein-like 27a CG134023-01 65 66 Negative Regulatorof Translation-like 28a CG134032-01 67 68 4E-binding Protein 2-like 29aCG134304-01 69 70 Hypothetical Intracellular Protein-like 30aCG134421-01 71 72 CAP-Gly domain containing protein-like 31a CC134895-0173 74 Differentiation Enhancing Factor 1-like 32a CG134922-01 75 76 C2domain containing protein-like 33a CG135070-01 77 78 Oxystyrol bindingprotein homolog-like 34a CG172478-01 79 80 Channel interacting PDZdomain-like 35a CG172549-01 81 82 Similar to SRC homology (SH3) andcysteine rich domain protein-like 35b CG172549-02 Similar to SRChomology (SH3) and cysteine rich domain protein-like 36a CG59828-01 8586 EDRK-rich factor 1-like 36b 172146552 87 88 EDRK-rich factor 1-like

[0029] Table A indicates the homology of NOVX polypeptides to knownprotein families. Thus, the nucleic acids and polypeptides, antibodiesand related compounds according to the invention corresponding to a NOVXas identified in column 1 of Table A will be useful in therapeutic anddiagnostic applications implicated in, for example, pathologies anddisorders associated with the known protein families identified incolumn 5 of Table A.

[0030] Pathologies, diseases, disorders and condition and the like thatare associated with NOVX sequences include, but are not limited to:e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heartdefects, aortic stenosis, atrial septal defect (ASD), atrioventricular(A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaorticstenosis, ventricular septal defect (VSD), valve diseases, tuberoussclerosis, scleroderma, obesity, metabolic disturbances associated withobesity, transplantation, adrenoleukodystrophy, congenital adrenalhyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm;adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia,hypercoagulation, idiopathic thrombocytopenic purpura,immunodeficiencies, graft versus host disease, AIDS, bronchial asthma,Crohn's disease; multiple sclerosis, treatment of Albright HereditaryOstoeodystrophy, infectious disease, anorexia, cancer-associatedcachexia, cancer, neurodegenerative disorders, Alzheimer's Disease,Parkinson's Disorder, immune disorders, hematopoietic disorders, and thevarious dyslipidemias, the metabolic syndrome X and wasting disordersassociated with chronic diseases and various cancers, as well asconditions such as transplantation and fertility.

[0031] NOVX nucleic acids and their encoded polypeptides are useful in avariety of applications and contexts. The various NOVX nucleic acids andpolypeptides according to the invention are useful as novel members ofthe protein families according to the presence of domains and sequencerelatedness to previously described proteins. Additionally, NOVX nucleicacids and polypeptides can also be used to identify proteins that aremembers of the family to which the NOVX polypeptides belong.

[0032] Consistent with other known members of the family of proteins,identified in column 5 of Table A, the NOVX polypeptides of the presentinvention show homology to, and contain domains that are characteristicof, other members of such protein families. Details of the sequencerelatedness and domain analysis for each NOVX are presented in ExampleA.

[0033] The NOVX nucleic acids and polypeptides can also be used toscreen for molecules, which inhibit or enhance NOVX activity orfunction. Specifically, the nucleic acids and polypeptides according tothe invention may be used as targets for the identification of smallmolecules that modulate or inhibit diseases associated with the proteinfamilies listed in Table A.

[0034] The NOVX nucleic acids and polypeptides are also useful fordetecting specific cell types. Details of the expression analysis foreach NOVX are presented in Example C. Accordingly, the NOVX nucleicacids, polypeptides, antibodies and related compounds according to theinvention will have diagnostic and therapeutic applications in thedetection of a variety of diseases with differential expression innormal vs. diseased tissues, e.g. detection of a variety of cancers.

[0035] Additional utilities for NOVX nucleic acids and polypeptidesaccording to the invention are disclosed herein.

[0036] NOVX Clones

[0037] NOVX nucleic acids and their encoded polypeptides are useful in avariety of applications and contexts. The various NOVX nucleic acids andpolypeptides according to the invention are useful as novel members ofthe protein families according to the presence of domains and sequencerelatedness to previously described proteins. Additionally, NOVX nucleicacids and polypeptides can also be used to identify proteins that aremembers of the family to which the NOVX polypeptides belong.

[0038] The NOVX genes and their corresponding encoded proteins areuseful for preventing, treating or ameliorating medical conditions,e.g., by protein or gene therapy. Pathological conditions can bediagnosed by determining the amount of the new protein in a sample or bydetermining the presence of mutations in the new genes. Specific usesare described for each of the NOVX genes, based on the tissues in whichthey are most highly expressed. Uses include developing products for thediagnosis or treatment of a variety of diseases and disorders.

[0039] The NOVX nucleic acids and proteins of the invention are usefulin potential diagnostic and therapeutic applications and as a researchtool. These include serving as a specific or selective nucleic acid orprotein diagnostic and/or prognostic marker, wherein the presence oramount of the nucleic acid or the protein are to be assessed, as well aspotential therapeutic applications such as the following: (i) a proteintherapeutic, (ii) a small molecule drug target, (iii) an antibody target(therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) anucleic acid useful in gene therapy (gene delivery/gene ablation), and(v) a composition promoting tissue regeneration in vitro and in vivo(vi) a biological defense weapon.

[0040] In one specific embodiment, the invention includes an isolatedpolypeptide comprising an amino acid sequence selected from the groupconsisting of: (a) a mature form of the amino acid sequence selectedfrom the group consisting of SEQ ID NO: 2n, wherein n is an integerbetween 1 and 44; (b) a variant of a mature form of the amino acidsequence selected from the group consisting of SEQ ID NO: 2n, wherein nis an integer between 1 and 44, wherein any amino acid in the matureform is changed to a different amino acid, provided that no more than15% of the amino acid residues in the sequence of the mature form are sochanged; (c) an amino acid sequence selected from the group consistingof SEQ ID NO: 2n, wherein n is an integer between 1 and 44; (d) avariant of the amino acid sequence selected from the group consisting ofSEQ ID NO:2n, wherein n is an integer between 1 and 44 wherein any aminoacid specified in the chosen sequence is changed to a different aminoacid, provided that no more than 15% of the amino acid residues in thesequence are so changed; and (e) a fragment of any of (a) through (d).

[0041] In another specific embodiment, the invention includes anisolated nucleic acid molecule comprising a nucleic acid sequenceencoding a polypeptide comprising an amino acid sequence selected fromthe group consisting of: (a) a mature form of the amino acid sequencegiven SEQ ID NO: 2n, wherein n is an integer between 1 and 44; (b) avariant of a mature form of the amino acid sequence selected from thegroup consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and44 wherein any amino acid in the mature form of the chosen sequence ischanged to a different amino acid, provided that no more than 15% of theamino acid residues in the sequence of the mature form are so changed;(c) the amino acid sequence selected from the group consisting of SEQ IDNO: 2n, wherein n is an integer between 1 and 44; (d) a variant of theamino acid sequence selected from the group consisting of SEQ ID NO: 2n,wherein n is an integer between 1 and 44, in which any amino acidspecified in the chosen sequence is changed to a different amino acid,provided that no more than 15% of the amino acid residues in thesequence are so changed; (e) a nucleic acid fragment encoding at least aportion of a polypeptide comprising the amino acid sequence selectedfrom the group consisting of SEQ ID NO: 2n, wherein n is an integerbetween 1 and 44 or any variant of said polypeptide wherein any aminoacid of the chosen sequence is changed to a different amino acid,provided that no more than 10% of the amino acid residues in thesequence are so changed; and (f) the complement of any of said nucleicacid molecules.

[0042] In yet another specific embodiment, the invention includes anisolated nucleic acid molecule, wherein said nucleic acid moleculecomprises a nucleotide sequence selected from the group consisting of:(a) the nucleotide sequence selected from the group consisting of SEQ IDNO: 2n-1, wherein n is an integer between 1 and 44; (b) a nucleotidesequence wherein one or more nucleotides in the nucleotide sequenceselected from the group consisting of SEQ ID NO: 2-n, wherein n is aninteger between 1 and 44 is changed from that selected from the groupconsisting of the chosen sequence to a different nucleotide providedthat no more than 15% of the nucleotides are so changed; (c) a nucleicacid fragment of the sequence selected from the group consisting of SEQID NO: 2n-1, wherein n is an integer between 1 and 44; and (d) a nucleicacid fragment wherein one or more nucleotides in the nucleotide sequenceselected from the group consisting of SEQ ID NO:2n-1, wherein n is aninteger between 1 and 44 is changed from that selected from the groupconsisting of the chosen sequence to a different nucleotide providedthat no more than 15% of the nucleotides are so changed.

[0043] NOVX Nucleic Acids and Polypeptides

[0044] One aspect of the invention pertains to isolated nucleic acidmolecules that encode NOVX polypeptides or biologically active portionsthereof. Also included in the invention are nucleic acid fragmentssufficient for use as hybridization probes to identify NOVX-encodingnucleic acids (e.g., NOVX mRNAs) and fragments for use as PCR primersfor the amplification and/or mutation of NOVX nucleic acid molecules. Asused herein, the term “nucleic acid molecule” is intended to include DNAmolecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA),analogs of the DNA or RNA generated using nucleotide analogs, andderivatives, fragments and homologs thereof. The nucleic acid moleculemay be single-stranded or double-stranded, but preferably is compriseddouble-stranded DNA.

[0045] A NOVX nucleic acid can encode a mature NOVX polypeptide. As usedherein, a “mature” form of a polypeptide or protein disclosed in thepresent invention is the product of a naturally occurring polypeptide orprecursor form or proprotein. The naturally occurring polypeptide,precursor or proprotein includes, by way of nonlimiting example, thefull-length gene product encoded by the corresponding gene.Alternatively, it may be defined as the polypeptide, precursor orproprotein encoded by an ORF described herein. The product “mature” formarises, by way of nonlimiting example, as a result of one or morenaturally occurring processing steps that may take place within the cell(e.g., host cell) in which the gene product arises. Examples of suchprocessing steps leading to a “mature” form of a polypeptide or proteininclude the cleavage of the N-terminal methionine residue encoded by theinitiation codon of an ORF, or the proteolytic cleavage of a signalpeptide or leader sequence. Thus a mature form arising from a precursorpolypeptide or protein that has residues 1 to N, where residue 1 is theN-terminal methionine, would have residues 2 through N remaining afterremoval of the N-terminal methionine. Alternatively, a mature formarising from a precursor polypeptide or protein having, residues 1 to N,in which an N-terminal signal sequence from residue 1 to residue M iscleaved, would have the residues from residue M+1 to residue Nremaining. Further as used herein, a “mature” form of a polypeptide orprotein may arise from a step of post-translational modification otherthan a proteolytic cleavage event. Such additional processes include, byway of non-limiting example, glycosylation, myristylation orphosphorylation. In general, a mature polypeptide or protein may resultfrom the operation of only one of these processes, or a combination ofany of them.

[0046] The term “probe”, as utilized herein, refers to nucleic acidsequences of variable length, preferably between at least about 10nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000nt, depending upon the specific use. Probes are used in the detection ofidentical, similar, or complementary nucleic acid sequences. Longerlength probes are generally obtained from a natural or recombinantsource, are highly specific, and much slower to hybridize thanshorter-length oligomer probes. Probes may be single-stranded ordouble-stranded and designed to have specificity in PCR, membrane-basedhybridization technologies, or ELISA-like technologies.

[0047] The term “isolated” nucleic acid molecule, as used herein, is anucleic acid that is separated from other nucleic acid molecules whichare present in the natural source of the nucleic acid. Preferably, an“isolated” nucleic acid is free of sequences which naturally flank thenucleic acid (i.e., sequences located at the 5′- and 3′-termini of thenucleic acid) in the genomic DNA of the organism from which the nucleicacid is derived. For example, in various embodiments, the isolated NOVXnucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flankthe nucleic acid molecule in genomic DNA of the cell/tissue from whichthe nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.).Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule,can be substantially free of other cellular material, or culture medium,or of chemical precursors or other chemicals.

[0048] A nucleic acid molecule of the invention, e.g., a nucleic acidmolecule having the nucleotide sequence of SEQ ID NO:2n-1, wherein n isan integer between 1 and 44, or a complement of this nucleotidesequence, can be isolated using standard molecular biology techniquesand the sequence information provided herein. Using all or a portion ofthe nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integerbetween 1 and 44, as a hybridization probe. NOVX molecules can beisolated using standard hybridization and cloning techniques (e.g., asdescribed in Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORYMANUAL 2^(nd) Ed., Cold Spring Harbor Laboratory Press, Cold SpringHarbor, N.Y. 1989; and Ausubel, et al., (eds.), CURRENT PROTOCOLS INMOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y., 1993.)

[0049] A nucleic acid of the invention can be amplified using cDNA, mRNAor alternatively, genomic DNA, as a template with appropriateoligonucleotide primers according to standard PCR amplificationtechniques. The nucleic acid so amplified can be cloned into anappropriate vector and characterized by DNA sequence analysis.Furthermore, oligonucleotides corresponding, to NOVX nucleotidesequences can be prepared by standard synthetic techniques, e.g. usingan automated DNA synthesizer.

[0050] As used herein, the term “oligonucleotide” refers to a series oflinked nucleotide residues. A short oligonucleotide sequence may bebased on, or designed from, a genomic or cDNA sequence and is used toamplify, confirm, or reveal the presence of an identical, similar orcomplementary DNA or RNA in a particular cell or tissue.Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. Inone embodiment of the invention, an oligonucleotide comprising a nucleicacid molecule less than 100 nt in length would further comprise at least6 contiguous nucleotides of SEQ ID NO:2n-1, wherein n is an integerbetween 1 and 44, or a complement thereof. Oligonucleotides may bechemically synthesized and may also be used as probes.

[0051] In another embodiment, an isolated nucleic acid molecule of theinvention comprises a nucleic acid molecule that is a complement of thenucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integerbetween 1 and 44, or a portion of this nucleotide sequence (e.g., afragment that can be used as a probe or primer or a fragment encoding abiologically-active portion of a NOVX polypeptide). A nucleic acidmolecule that is complementary to the nucleotide sequence of SEQ IDNO:2n-1, wherein n is an integer between 1 and 44, is one that issufficiently complementary to the nucleotide sequence of SEQ ID NO:2n-1,wherein n is an integer between 1 and 44, that it can hydrogen bond withfew or no mismatches to the nucleotide sequence shown in SEQ ID NO:2n-1,wherein n is an integer between 1 and 44, thereby forming, a stableduplex.

[0052] As used herein, the term “complementary” refers to Watson-Crickor Hoogsteen base pairing between nucleotides units of a nucleic acidmolecule, and the term “binding” means the physical or chemicalinteraction between two polypeptides or compounds or associatedpolypeptides or compounds or combinations thereof. Binding, includesionic, non-ionic, van der Waals, hydrophobic interactions, and the like.A physical interaction can be either direct or indirect. Indirectinteractions may be through or due to the effects of another polypeptideor compound. Direct binding refers to interactions that do not takeplace through, or due to, the effect of another polypeptide or compound,but instead are without other substantial chemical intermediates.

[0053] A “fragment” provided herein is defined as a sequence of at least6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, alength sufficient to allow for specific hybridization in the case ofnucleic acids or for specific recognition of an epitope in the case ofamino acids, and is at most some portion less than a full lengthsequence. Fragments may be derived from any contiguous portion of anucleic acid or amino acid sequence of choice.

[0054] A full-length NOVX clone is identified as containing an ATGtranslation start codon and an in-frame stop codon. Any disclosed NOVXnucleotide sequence lacking an ATG start codon therefore encodes atruncated C-terminal fragment of the respective NOVX polypeptide, andrequires that the corresponding full-length cDNA extend in the 5′direction of the disclosed sequence. Any disclosed NOVX nucleotidesequence lacking an in-frame stop codon similarly encodes a truncatedN-terminal fragment of the respective NOVX polypeptide, and requiresthat the corresponding full-length cDNA extend in the 3′ direction ofthe disclosed sequence.

[0055] A “derivative” is a nucleic acid sequence or amino acid sequenceformed from the native compounds either directly, by modification orpartial substitution. An “analog” is a nucleic acid sequence or aminoacid sequence that has a structure similar to, but not identical to, thenative compound, e.g. they differs from it in respect to certaincomponents or side chains. Analogs may be synthetic or derived from adifferent evolutionary origin and may have a similar or oppositemetabolic activity compared to wild type. A “homolog” is a nucleic acidsequence or amino acid sequence of a particular gene that is derivedfrom different species.

[0056] Derivatives and analogs may be full length or other than fulllength. Derivatives or analogs of the nucleic acids or proteins of theinvention include, but are not limited to, molecules comprising regionsthat are substantially homologous to the nucleic acids or proteins ofthe invention, in various embodiments, by at least about 70%, 80%, or95% identity (with a preferred identity of 80-95%) over a nucleic acidor amino acid sequence of identical size or when compared to an alignedsequence in which the alignment is done by a computer homology programknown in the art, or whose encoding nucleic acid is capable ofhybridizing to the complement of a sequence encoding the proteins understringent, moderately stringent, or low stringent conditions. See e.g.Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley &Sons, New York, N.Y. 1993, and below.

[0057] A “homologous nucleic acid sequence” or “homologous amino acidsequence,” or variations thereof, refer to sequences characterized by ahomology at the nucleotide level or amino acid level as discussed above.Homologous nucleotide sequences include those sequences coding forisoforms of NOVX polypeptides. Isoforms can be expressed in differenttissues of the same organism as a result of, for example, alternativesplicing of RNA. Alternatively, isoforms can be encoded by differentgenes. In the invention, homologous nucleotide sequences includenucleotide sequences encoding for a NOVX polypeptide of species otherthan humans, including, but not limited to: vertebrates, and thus caninclude, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and otherorganisms. Homologous nucleotide sequences also include, but are notlimited to, naturally occurring allelic variations and mutations of thenucleotide sequences set forth herein. A homologous nucleotide sequencedoes not, however, include the exact nucleotide sequence encoding humanNOVX protein. Homologous nucleic acid sequences include those nucleicacid sequences that encode conservative amino acid substitutions (seebelow) in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, aswell as a polypeptide possessing NOVX biological activity. Variousbiological activities of the NOVX proteins are described below.

[0058] A NOVX polypeptide is encoded by the open reading frame (“ORF”)of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence thatcould potentially be translated into a polypeptide. A stretch of nucleicacids comprising an ORF is uninterrupted by a stop codon. An ORF thatrepresents the coding sequence for a full protein begins with an ATG“start” codon and terminates with one of the three “stop” codons,namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF maybe any part of a coding sequence, with or without a start codon, a stopcodon, or both. For an ORF to be considered as a good candidate forcoding for a bona fide cellular protein, a minimum size requirement isoften set, e.g., a stretch of DNA that would encode a protein of 50amino acids or more.

[0059] The nucleotide sequences determined from the cloning of the humanNOVX genes allows for the generation of probes and primers designed foruse in identifying and/or cloning NOVX homologues in other cell types,e.g. from other tissues, as well as NOVX homologues from othervertebrates. The probe/primer typically comprises substantially purifiedoligonucleotide. The oligonucleotide typically comprises a region ofnucleotide sequence that hybridizes under stringent conditions to atleast about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutivesense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is aninteger between 1 and 44; or an anti-sense strand nucleotide sequence ofSEQ ID NO:2n-1, wherein n is an integer between 1 and 44; or of anaturally occurring mutant of SEQ ID NO:2n-1, wherein n is an integerbetween 1 and 44.

[0060] Probes based on the human NOVX nucleotide sequences can be usedto detect transcripts or genomic sequences encoding the same orhomologous proteins. In various embodiments, the probe has a detectablelabel attached, e.g. the label can be a radioisotope, a fluorescentcompound, an enzyme, or an enzyme co-factor. Such probes can be used asa part of a diagnostic test kit for identifying cells or tissues whichmis-express a NOVX protein, such as by measuring a level of aNOVX-encoding nucleic acid in a sample of cells from a subject e.g.,detecting NOVX mRNA levels or determining whether a genomic NOVX genehas been mutated or deleted.

[0061] “A polypeptide having a biologically-active portion of a NOVXpolypeptide” refers to polypeptides exhibiting activity similar, but notnecessarily identical to, an activity of a polypeptide of the invention,including mature forms, as measured in a particular biological assay,with or without dose dependency. A nucleic acid fragment encoding a“biologically-active portion of NOVX” can be prepared by isolating aportion of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44,that encodes a polypeptide having a NOVX biological activity (thebiological activities of the NOVX proteins are described below),expressing the encoded portion of NOVX protein (e.g., by recombinantexpression in vitro) and assessing the activity of the encoded portionof NOVX.

[0062] NOVX Nucleic Acid and Polypeptide Variants

[0063] The invention further encompasses nucleic acid molecules thatdiffer from the nucleotide sequences of SEQ ID NO:2n-1, wherein n is aninteger between 1 and 44, due to degeneracy of the genetic code and thusencode the same NOVX proteins as that encoded by the nucleotidesequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.In another embodiment, an isolated nucleic acid molecule of theinvention has a nucleotide sequence encoding a protein having an aminoacid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

[0064] In addition to the human NOVX nucleotide sequences of SEQ IDNO:2n-1, wherein n is an integer between 1 and 44, it will beappreciated by those skilled in the art that DNA sequence polymorphismsthat lead to changes in the amino acid sequences of the NOVXpolypeptides may exist within a population (e.g., the human population).Such genetic polymorphism in the NOVX genes may exist among individualswithin a population due to natural allelic variation. As used herein,the terms “gene” and “recombinant gene” refer to nucleic acid moleculescomprising an open reading frame (ORF) encoding a NOVX protein,preferably a vertebrate NOVX protein. Such natural allelic variationscan typically result in 1-5% variance in the nucleotide sequence of theNOVX genes. Any and all such nucleotide variations and resulting aminoacid polymorphisms in the NOVX polypeptides, which are the result ofnatural allelic variation and that do not alter the functional activityof the NOVX polypeptides, are intended to be within the scope of theinvention.

[0065] Moreover, nucleic acid molecules encoding NOVX proteins fromother species, and thus that have a nucleotide sequence that differsfrom a human SEQ ID NO:2n-1, wherein n is an integer between 1 and 44,are intended to be within the scope of the invention. Nucleic acidmolecules corresponding to natural allelic variants and homologues ofthe NOVX cDNAs of the invention can be isolated based on their homologyto the human NOVX nucleic acids disclosed herein using the human cDNAs,or a portion thereof, as a hybridization probe according to standardhybridization techniques under stringent hybridization conditions.

[0066] Accordingly, in another embodiment, an isolated nucleic acidmolecule of the invention is at least 6 nucleotides in length andhybridizes under stringent conditions to the nucleic acid moleculecomprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is aninteger between 1 and 44. In another embodiment, the nucleic acid is atleast 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or morenucleotides in length. In yet another embodiment, an isolated nucleicacid molecule of the invention hybridizes to the coding region. As usedherein, the term “hybridizes under stringent conditions” is intended todescribe conditions for hybridization and washing under which nucleotidesequences at least about 65% homologous to each other typically remainhybridized to each other.

[0067] Homologs (i.e., nucleic acids encoding NOVX proteins derived fromspecies other than human) or other related sequences (e.g., paralogs)can be obtained by low, moderate or high stringency hybridization withall or a portion of the particular human sequence as a probe usingmethods well known in the art for nucleic acid hybridization andcloning.

[0068] As used herein, the phrase “stringent hybridization conditions”refers to conditions under which a probe, primer or oligonucleotide willhybridize to its target sequence, but to no other sequences. Stringentconditions are sequence-dependent and will be different in differentcircumstances. Longer sequences hybridize specifically at highertemperatures than shorter sequences. Generally, stringent conditions areselected to be about 5° C. lower than the thermal melting point (Tm) forthe specific sequence at a defined ionic strength and pH. The Tm is thetemperature (under defined ionic strength, pH and nucleic acidconcentration) at which 50% of the probes complementary to the targetsequence hybridize to the target sequence at equilibrium. Since thetarget sequences are generally present at excess, at Tm, 50% of theprobes are occupied at equilibrium. Typically, stringent conditions willbe those in which the salt concentration is less than about 1.0 M sodiumion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0to 8.3 and the temperature is at least about 30° C. for short probes,primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about60° C. for longer probes, primers and oligonucleotides. Stringentconditions may also be achieved with the addition of destabilizingagents, such as formamide.

[0069] Stringent conditions are known to those skilled in the art andcan be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULARBIOLOGY, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, theconditions are such that sequences at least about 65%, 70%, 75%, 85%,90%, 95%, 98%, or 99% homologous to each other typically remainhybridized to each other. A non-limiting example of stringenthybridization conditions are hybridization in a high salt buffercomprising 6× SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02%Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C.,followed by one or more washes in 0.2× SSC, 0.01% BSA at 50° C. Anisolated nucleic acid molecule of the invention that hybridizes understringent conditions to a sequence of SEQ ID NO:2n-1, wherein n is aninteger between 1 and 44, corresponds to a naturally-occurring nucleicacid molecule. As used herein, a “naturally-occurring” nucleic acidmolecule refers to an RNA or DNA molecule having a nucleotide sequencethat occurs in nature (e.g., encodes a natural protein).

[0070] In a second embodiment, a nucleic acid sequence that ishybridizable to the nucleic acid molecule comprising the nucleotidesequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, orfragments, analogs or derivatives thereof, under conditions of moderatestringency is provided. A non-limiting example of moderate stringencyhybridization conditions are hybridization in 6× SSC, 5× Reinhardt'ssolution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C.followed by one or more washes in 1× SSC, 0.1% SDS at 37° C. Otherconditions of moderate stringency that may be used are well-known withinthe art. See, e.g. Ausubel, et al (eds.), 1993, CURRENT PROTOCOLS INMOLECULAR BIOLOGY, John Wiley & Sons, NY, and Krieger, 1990; GENETRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.

[0071] In a third embodiment, a nucleic acid that is hybridizable to thenucleic acid molecule comprising the nucleotide sequences of SEQ IDNO:2n-1, wherein n is an integer between 1 and 44, or fragments, analogsor derivatives thereof, under conditions of low stringency, is provided.A non-limiting, example of low stringency hybridization conditions arehybridization in 35% formamide, 5× SSC, 50 mM Tris-HCl (pH 7.5), 5 mMEDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmonsperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one ormore washes in 2× SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDSat 50° C. Other conditions of low stringency that may be used are wellknown in the art (e.g., as employed for cross-species hybridizations).See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULARBIOLOGY, John Wiley & Sons. NY, and Kriegler, 1990, GENE TRANSFER ANDEXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg,1981, Proc Natl Acad Sci USA 78: 6789-6792.

[0072] Conservative Mutations

[0073] In addition to naturally-occurring allelic variants of NOVXsequences that may exist in the population, the skilled artisan willfurther appreciate that changes can be introduced by mutation into thenucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between1 and 44, thereby leading to changes in the amino acid sequences of theencoded NOVX protein, without altering the functional ability of thatNOVX protein. For example, nucleotide substitutions leading to aminoacid substitutions at “non-essential” amino acid residues can be made inthe sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44.A “non-essential” amino acid residue is a residue that can be alteredfrom the wild-type sequences of the NOVX proteins without altering theirbiological activity, whereas an “essential” amino acid residue isrequired for such biological activity. For example, amino acid residuesthat are conserved among the NOVX proteins of the invention arepredicted to be particularly non-amenable to alteration. Amino acids forwhich conservative substitutions can be made are well-known within theart.

[0074] Another aspect of the invention pertains to nucleic acidmolecules encoding NOVX proteins that contain changes in amino acidresidues that are not essential for activity. Such NOVX proteins differin amino acid sequence from SEQ ID NO:2n-1, wherein n is an integerbetween 1 and 44, yet retain biological activity. In one embodiment, theisolated nucleic acid molecule comprises a nucleotide sequence encodinga protein, wherein the protein comprises an amino acid sequence at leastabout 40% homologous to the amino acid sequences of SEQ ID NO:2n,wherein n is an integer between 1 and 44. Preferably, the proteinencoded by the nucleic acid molecule is at least about 60% homologous toSEQ ID NO:2n, wherein n is an integer between 1 and 44; more preferablyat least about 70% homologous to SEQ ID NO:2n, wherein n is an integerbetween 1 and 44; still more preferably at least about 80% homologous toSEQ ID NO:2n, wherein n is an integer between 1 and 44; even morepreferably at least about 90% homologous to SEQ ID NO:2n, wherein n isan integer between 1 and 44; and most preferably at least about 95%homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44.

[0075] An isolated nucleic acid molecule encoding a NOVX proteinhomologous to the protein of SEQ ID NO:2n, wherein n is an integerbetween 1 and 44, can be created by introducing one or more nucleotidesubstitutions, additions or deletions into the nucleotide sequence ofSEQ ID NO:2n-1, wherein n is an integer between 1 and 44, such that oneor more amino acid substitutions, additions or deletions are introducedinto the encoded protein.

[0076] Mutations can be introduced any one of SEQ ID NO:2n-1, wherein nis an integer between 1 and 44, by standard techniques, such assite-directed mutagenesis and PCR-mediated mutagenesis. Preferably,conservative amino acid substitutions are made at one or more predicted,non-essential amino acid residues. A “conservative amino acidsubstitution” is one in which the amino acid residue is replaced with anamino acid residue having a similar side chain. Families of amino acidresidues having similar side chains have been defined within the art.These families include amino acids with basic side chains (e.g. lysine,arginine, histidine), acidic side chains (e.g. aspartic acid, glutamicacid), uncharged polar side chains (e.g., glycine, asparagine,glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains(e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine,methionine, tryptophan), beta-branched side chains (e.g. threonine,valine, isoleucine) and aromatic side chains (e.g., tyrosine,phenylalanine, tryptophan, histidine). Thus, a predicted non-essentialamino acid residue in the NOVX protein is replaced with another aminoacid residue from the same side chain family. Alternatively, in anotherembodiment, mutations can be introduced randomly along all or part of aNOVX coding sequence, such as by saturation mutagenesis, and theresultant mutants can be screened for NOVX biological activity toidentify mutants that retain activity. Following mutagenesis of anucleic acid of SEQ ID NO:2n-1, wherein n is an integer between 1 and44, the encoded protein can be expressed by any recombinant technologyknown in the art and the activity of the protein can be determined.

[0077] The relatedness of amino acid families may also be determinedbased on side chain interactions. Substituted amino acids may be fullyconserved “strong” residues or fully conserved “weak” residues. The“strong” group of conserved amino acid residues may be any one of thefollowing (groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW,wherein the single letter amino acid codes are grouped by those aminoacids that may be substituted for each other. Likewise, the “weak” groupof conserved residues may be any one of the following: CSA, ATV, SAG,STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letterswithin each group represent the single letter amino acid code.

[0078] In one embodiment, a mutant NOVX protein can be assayed for (i)the ability to form protein:protein interactions with other NOVXproteins, other cell-surface proteins, or biologically-active portionsthereof, (ii) complex formation between a mutant NOVX protein and a NOVXligand; or (iii) the ability of a mutant NOVX protein to bind to anintracellular target protein or biologically-active portion thereof;(e.g. avidin proteins).

[0079] In yet another embodiment, a mutant NOVX protein can be assayedfor the ability to regulate a specific biological function (e.g.,regulation of insulin release).

[0080] Antisense Nucleic Acids

[0081] Another aspect of the invention pertains to isolated antisensenucleic acid molecules that are hybridizable to or complementary to thenucleic acid molecule comprising the nucleotide sequence of SEQ IDNO:2n-1, wherein n is an integer between 1 and 44, or fragments, analogsor derivatives thereof. An “antisense” nucleic acid comprises anucleotide sequence that is complementary to a “sense” nucleic acidencoding a protein (e.g. complementary to the coding strand of adouble-stranded cDNA molecule or complementary to an mRNA sequence). Inspecific aspects, antisense nucleic acid molecules are provided thatcomprise a sequence complementary to at least about 10, 25, 50, 100, 250or 500 nucleotides or an entire NOVX coding strand, or to only a portionthereof. Nucleic acid molecules encoding fragments, homologs,derivatives and analogs of a NOVX protein of SEQ ID NO:2n, wherein n isan integer between 1 and 44, or antisense nucleic acids complementary toa NOVX nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integerbetween 1 and 44, are additionally provided.

[0082] In one embodiment, an antisense nucleic acid molecule isantisense to a “coding region” of the coding strand of a nucleotidesequence encoding a NOVX protein. The term “coding region” refers to theregion of the nucleotide sequence comprising codons which are translatedinto amino acid residues. In another embodiment, the antisense nucleicacid molecule is antisense to a “noncoding region” of the coding strandof a nucleotide sequence encoding the NOVX protein. The term “noncodingregion” refers to 5′ and 3′ sequences which flank the coding region thatare not translated into amino acids (i.e., also referred to as 5′ and 3′untranslated regions).

[0083] Given the coding strand sequences encoding the NOVX proteindisclosed herein, antisense nucleic acids of the invention can bedesigned according to the rules of Watson and Crick or Hoogsteen basepairing. The antisense nucleic acid molecule can be complementary to theentire coding region of NOVX mRNA, but more preferably is anoligonucleotide that is antisense to only a portion of the coding ornoncoding region of NOVX mRNA. For example, the antisenseoligonucleotide can be complementary to the region surrounding thetranslation start site of NOVX mRNA. An antisense oligonucleotide canbe, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50nucleotides in length. An antisense nucleic acid of the invention can beconstructed using chemical synthesis or enzymatic ligation reactionsusing procedures known in the art. For example, an antisense nucleicacid (e.g. an antisense oligonucleotide) can be chemically synthesizedusing naturally-occurring nucleotides or variously modified nucleotidesdesigned to increase the biological stability of the molecules or toincrease the physical stability of the duplex formed between theantisense and sense nucleic acids (e.g. phosphorothioate derivatives andacridine substituted nucleotides can be used).

[0084] Examples of modified nucleotides that can be used to generate theantisense nucleic acid include: 5-fluorouracil, 5-bromouracil,5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine,5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl)uracil, 5-carboxymethylaminomethyluracil, dihydrouracil,beta-D-galactosylqueosine, inosine, N6-isopentenyladenine,1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine,2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine,N6-adenine, 7-methylguanine, 5-methylaminomethyluracil,5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil,beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil,2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v),wybutoxosine, pseudouracil, queosine, 2-thiocytosine,5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acidmethylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil,3-(3-amino-3-N-2-carboxypropyl)uracil, (acp3)w, and 2,6-diaminopurine.Alternatively, the antisense nucleic acid can be produced biologicallyusing an expression vector into which a nucleic acid has been subclonedin an antisense orientation (i.e. RNA transcribed from the insertednucleic acid will be of an antisense orientation to a target nucleicacid of interest, described further in the following subsection).

[0085] The antisense nucleic acid molecules of the invention aretypically administered to a subject or generated in situ such that theyhybridize with or bind to cellular mRNA and/or genomic DNA encoding aNOVX protein to thereby inhibit expression of the protein (e.g. byinhibiting transcription and/or translation). The hybridization can beby conventional nucleotide complementarity to form a stable duplex, or,for example, in the case of an antisense nucleic acid molecule thatbinds to DNA duplexes, through specific interactions in the major grooveof the double helix. An example of a route of administration ofantisense nucleic acid molecules of the invention includes directinjection at a tissue site. Alternatively, antisense nucleic acidmolecules can be modified to target selected cells and then administeredsystemically. For example, for systemic administration, antisensemolecules can be modified such that they specifically bind to receptorsor antigens expressed on a selected cell surface (e.g., by linking theantisense nucleic acid molecules to peptides or antibodies that bind tocell surface receptors or antigens). The antisense nucleic acidmolecules can also be delivered to cells using the vectors describedherein. To achieve sufficient nucleic acid molecules, vector constructsin which the antisense nucleic acid molecule is placed under the controlof a strong pol II or pol III promoter are preferred.

[0086] In yet another embodiment, the antisense nucleic acid molecule ofthe invention is an -anomeric nucleic acid molecule. An -anomericnucleic acid molecule forms specific double-stranded hybrids withcomplementary RNA in which, contrary to the usual -units, the strandsrun parallel to each other. See, e.g., Gaultier, et al., 1987, NuclAcids Res 15: 6625-6641. The antisense nucleic acid molecule can alsocomprise a 2′-o-methylribonucleotide (See, e.g. Inoue, et al. 1987,Nucl. Acids Res 15: 6131-6148) or a chimeric RNA-DNA analogue (See. e.g.Inoue, et al., 1987, FEBS Lett. 215: 327-330.

[0087] Ribozymes and PNA Moieties

[0088] Nucleic acid modifications include, by way of non-limitingexample, modified bases, and nucleic acids whose sugar phosphatebackbones are modified or derivatized. These modifications are carriedout at least in part to enhance the chemical stability of the modifiednucleic acid, such that they may be used, for example, as antisensebinding nucleic acids in therapeutic applications in a subject.

[0089] In one embodiment, an antisense nucleic acid of the invention isa ribozyme. Ribozymes are catalytic RNA molecules with ribonucleaseactivity that are capable of cleaving a single-stranded nucleic acid,such as an mRNA, to which they have a complementary region. Thus,ribozymes (e.g., hammerhead ribozymes as described in Haselhoff andGerlach 1988, Nature 334: 585-591) can be used to catalytically cleaveNOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. Aribozyme having specificity for a NOVX-encoding nucleic acid can bedesigned based upon the nucleotide sequence of a NOVX cDNA disclosedherein (i.e., SEQ ID NO:2n-1, wherein n is an integer between 1 and 44).For example, a derivative of a Tetrahymena L-19 IVS RNA can beconstructed in which the nucleotide sequence of the active site iscomplementary to the nucleotide sequence to be cleaved in aNOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et al.and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also be usedto select a catalytic RNA having a specific ribonuclease activity from apool of RNA molecules. See, e.g., Bartel et al., (1993) Science261:1411-1418.

[0090] Alternatively, NOVX gene expression can be inhibited by targetingnucleotide sequences complementary to the regulatory region of the NOVXnucleic acid (e.g., the NOVX promoter and/or enhancers) to form triplehelical structures that prevent transcription of the NOVX gene in targetcells. See e.g. Helene, 1991, Anticancer Drug Des. 6: 569-84; Helene, etal. 1992 Ann. N.Y. Acad Sci 660: 27-36; Maher, 1992, Bioassays 14:807-15.

[0091] In various embodiments, the NOVX nucleic acids can be modified atthe base moiety, sugar moiety or phosphate backbone to improve, e.g. thestability, hybridization, or solubility of the molecule. For example,the deoxyribose phosphate backbone of the nucleic acids can be modifiedto generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996,Bioorg Med Chem 4: 5-23. As used herein, the terms “peptide nucleicacids” or “PNAs” refer to nucleic acid mimics (e.g. DNA mimics) in whichthe deoxyribose phosphate backbone is replaced by a pseudopeptidebackbone and only the four natural nucleotide bases are retained. Theneutral backbone of PNAs has been shown to allow for specifichybridization to DNA and RNA under conditions of low ionic strength. Thesynthesis of PNA oligomer can be performed using standard solid phasepeptide synthesis protocols as described in Hyrup, et al., 1996, supra;Perry-O'Keefe, et al., 1996, Proc. Natl Acad. Sci. USA 93: 14670-14675.

[0092] PNAs of NOVX can be used in therapeutic and diagnosticapplications. For example. PNAs can be used as antisense or antigeneagents for sequence-specific modulation of gene expression by, e.g.,inducing transcription or translation arrest or inhibiting replication.PNAs of NOVX can also be used, for example, in the analysis of singlebase pair mutations in a gene (e.g., PNA directed PCR clamping: asartificial restriction enzymes when used in combination with otherenzymes, e.g., S₁ nucleases (See, Hyrup, et al., 1996, supra); or asprobes or primers for DNA sequence and hybridization (see, Hyrup, etal., 1996, supra; Perry-O'Keefe, et al., 1996, supra).

[0093] In another embodiment, PNAs of NOVX can be modified, e.g., toenhance their stability or cellular uptake, by attaching lipophilic orother helper groups to PNA, by the formation of PNA-DNA chimeras, or bythe use of liposomes or other techniques of drug delivery known in theart. For example, PNA-DNA chimeras of NOVX can be generated that maycombine the advantageous properties of PNA and DNA. Such chimeras allowDNA recognition enzymes (e.g. RNase H and DNA polymerases) to interactwith the DNA portion while the PNA portion would provide high bindingaffinity and specificity. PNA-DNA chimeras can be linked using linkersof appropriate lengths selected in terms of base stacking, number ofbonds between the nucleotide bases, and orientation (see, Hyrup, et al.,1996, supra). The synthesis of PNA-DNA chimeras can be performed asdescribed in Hyrup, et al. 1996, supra and Finn, et al., 1996, NuclAcids Res 24: 3357-3363. For example, a DNA chain can be synthesized ona solid support using standard phosphoramidite coupling chemistry, andmodified nucleoside analogs, e.g.,5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can beused between the PNA and the 5′ end of DNA. See, e.g. Mag, et al., 1989,Nucl Acid Res 17: 5973-5988. PNA monomers are then coupled in a stepwisemanner to produce a chimeric molecule with a 5′ PNA sediment and a 3′DNA segment. See, e.g., Finn, et al., 1996, supra. Alternatively,chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNAsegment. See, e.g. Petersen, et al., 1975, Bioorg Med Chem Lett 5:1119-11124.

[0094] In other embodiments, the oligonucleotide may include otherappended groups such as peptides (e.g., for targeting host cellreceptors in vivo), or agents facilitating transport across the cellmembrane (see, e.g. Letsinger, et al., 1989, Proc Natl. Acad. Sci.U.S.A. 86: 6553-6556; Lemaitre, et al., 1987, Proc. Natl. Acad. Sci. 84:648-652; PCT Publication No. WO88/09810) or the blood-brain barrier(see, e.g., PCT Publication No. WO 89/10134). In addition,oligonucleotides can be modified with hybridization triggered cleavageagents (see, e.g. Krol, et al., 1988, BioTechniques 6:958-976) orintercalating agents (see, e.g. Zon, 1988, Pharm. Res. 5: 539-549). Tothis end, the oligonucleotide may be conjugated to another molecule,e.g., a peptide, a hybridization triggered cross-linking agent, atransport agent, a hybridization-triggered cleavage agent, and the like.

[0095] NOVX Polypeptides

[0096] A polypeptide according to the invention includes a polypeptideincluding the amino acid sequence of NOVX polypeptides whose sequencesare provided in any one of SEQ ID NO:2n, wherein n is an integer between1 and 44. The invention also includes a mutant or variant protein any ofwhose residues may be changed from the corresponding residues shown inany one of SEQ ID NO:2n, wherein n is an integer between 1 and 44, whilestill encoding a protein that maintains its NOVX activities andphysiological functions, or a functional fragment thereof.

[0097] In general, a NOVX variant that preserves NOVX-like functionincludes any variant in which residues at a particular position in thesequence have been substituted by other amino acids, and further includethe possibility of inserting an additional residue or residues betweentwo residues of the parent protein as well as the possibility ofdeleting one or more residues from the parent sequence. An amino acidsubstitution, insertion, or deletion is encompassed by the invention. Infavorable circumstances, the substitution is a conservative substitutionas defined above.

[0098] One aspect of the invention pertains to isolated NOVX proteins,and biologically-active portions thereof, or derivatives, fragments,analogs or homologs thereof. Also provided are polypeptide fragmentssuitable for use as immunogens to raise anti-NOVX antibodies. In oneembodiment, native NOVX proteins can be isolated from cells or tissuesources by an appropriate purification scheme using standard proteinpurification techniques. In another embodiment, NOVX proteins areproduced by recombinant DNA techniques. Alternative to recombinantexpression, a NOVX protein or polypeptide can be synthesized chemicallyusing standard peptide synthesis techniques.

[0099] An “isolated” or “purified” polypeptide or protein orbiologically-active portion thereof is substantially, free of cellularmaterial or other contaminating proteins from the cell or tissue sourcefrom which the NOVX protein is derived, or substantially free fromchemical precursors or other chemicals when chemically synthesized. Thelanguage “substantially free of cellular material” includes preparationsof NOVX proteins in which the protein is separated from cellularcomponents of the cells from which it is isolated orrecombinantly-produced. In one embodiment, the language “substantiallyfree of cellular material” includes preparations of NOVX proteins havingless than about 30% (by dry weight) of non-NOVX proteins (also referredto herein as a “contaminating protein”), more preferably less than about20% of non-NOVX proteins, still more preferably less than about 10% ofnon-NOVX proteins, and most preferably less than about 5% of non-NOVXproteins. When the NOVX protein or biologically-active portion thereofis recombinantly-produced, it is also preferably substantially free ofculture medium, i.e., culture medium represents less than about 20%,more preferably less than about 10%, and most preferably less than about5% of the volume of the NOVX protein preparation.

[0100] The language “substantially free of chemical precursors or otherchemicals” includes preparations of NOVX proteins in which the proteinis separated from chemical precursors or other chemicals that areinvolved in the synthesis of the protein. In one embodiment, thelanguage “substantially free of chemical precursors or other chemicals”includes preparations of NOVX proteins having less than about 30% (bydry weight) of chemical precursors or non-NOVX chemicals, morepreferably less than about 20% chemical precursors or non-NOVXchemicals, still more preferably less than about 10% chemical precursorsor non-NOVX chemicals, and most preferably less than about 5% chemicalprecursors or non-NOVX chemicals.

[0101] Biologically-active portions of NOVX proteins include peptidescomprising amino acid sequences sufficiently homologous to or derivedfrom the amino acid sequences of the NOVX proteins (e.g. the amino acidsequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44) thatinclude fewer amino acids than the full-length NOVX proteins, andexhibit at least one activity of a NOVX protein. Typically,biologically-active portions comprise a domain or motif with at leastone activity of the NOVX protein. A biologically-active portion of aNOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100or mote amino acid resides in length.

[0102] Moreover, other biologically-active portions in which otherregions of the protein are deleted, can be prepared by recombinanttechniques and evaluated for one or more of the functional activities ofa native NOVX protein.

[0103] In an embodiment, the NOVX protein has an amino acid sequence ofSEQ ID NO:2n, wherein n is an integer between 1 and 44. In otherembodiments, the NOVX protein is substantially homologous to SEQ IDNO:2n, wherein n is an integer between 1 and 44, and retains thefunctional activity of the protein of SEQ ID NO:2n, wherein n is aninteger between 1 and 44, yet differs in amino acid sequence due tonatural allelic variation or mutagenesis, as described in detail, below.Accordingly, in another embodiment, the NOVX protein is a protein thatcomprises an amino acid sequence at least about 45% homologous to theamino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1and 44, and retains the functional activity of the NOVX proteins of SEQID NO:2n, wherein n is an integer between 1 and 44.

[0104] Determining Homology Between Two or More Sequences

[0105] To determine the percent homology of two amino acid sequences orof two nucleic acids, the sequences are aligned for optimal comparisonpurposes (e.g. gaps can be introduced in the sequence of a first aminoacid or nucleic acid sequence for optimal alignment with a second aminoor nucleic acid sequence). The amino acid residues or nucleotides atcorresponding amino acid positions or nucleotide positions are thencompared. When a position in the first sequence is occupied by the sameamino acid residue or nucleotide as the corresponding position in thesecond sequence, then the molecules are homologous at that position(i.e., as used herein amino acid or nucleic acid “homology” isequivalent to amino acid or nucleic acid “identity”).

[0106] The nucleic acid sequence homology may be determined as thedegree of identity between two sequences. The homology may be determinedusing computer programs known in the art, such as GAP software providedin the GCG program package. See, Needleman and Wunsch, 1970, J Mol Biol48: 443-453. Using GCG GAP software with the following settings fornucleic acid sequence comparison: GAP creation penalty of 5.0 and GAPextension penalty of 0.3, the coding region of the analogous nucleicacid sequences referred to above exhibits a degree of identitypreferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, withthe CDS (encoding) part of the DNA sequence of SEQ ID NO:2n-1, wherein nis an integer between 1 and 44.

[0107] The term “sequence identity” refers to the degree to which twopolynucleotide or polypeptide sequences are identical on aresidue-by-residue basis over a particular region of comparison. Theterm “percentage of sequence identity” is calculated by comparing twooptimally aligned sequences over that region of comparison, determiningthe number of positions at which the identical nucleic acid base (e.g.A, T, C, G, U, or I, in the case of nucleic acids) occurs in bothsequences to yield the number of matched positions, dividing the numberof matched positions by the total number of positions in the region ofcomparison (i.e., the window size), and multiplying the result by 100 toyield the percentage of sequence identity. The term “substantialidentity” as used herein denotes a characteristic of a polynucleotidesequence, wherein the polynucleotide comprises a sequence that has atleast 80 percent sequence identity, preferably at least 85 percentidentity and often 90 to 95 percent sequence identity, more usually atleast 99 percent sequence identity as compared to a reference sequenceover a comparison region.

[0108] Chimeric and Fusion Proteins

[0109] The invention also provides NOVX chimeric or fusion proteins. Asused herein, a NOVX “chimeric protein” or “fusion protein” comprises aNOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVXpolypeptide” refers to a polypeptide having an amino acid sequencecorresponding to a NOVX protein of SEQ ID NO:2n, wherein n is an integerbetween 1 and 44, whereas a “non-NOVX polypeptide” refers to apolypeptide having an amino acid sequence corresponding to a proteinthat is not substantially homologous to the NOVX protein, e.g., aprotein that is different from the NOVX protein and that is derived fromthe same or a different organism. Within a NOVX fusion protein the NOVXpolypeptide can correspond to all or a portion of a NOVX protein. In oneembodiment, a NOVX fusion protein comprises at least onebiologically-active portion of a NOVX protein. In another embodiment, aNOVX fusion protein comprises at least two biologically-active portionsof a NOVX protein. In yet another embodiment, a NOVX fusion proteincomprises at least three biologically-active portions of a NOVX protein.Within the fusion protein, the term “operatively-linked” is intended toindicate that the NOVX polypeptide and the non-NOVX polypeptide arefused in-frame with one another. The non-NOVX polypeptide can be fusedto the N-terminus or C-terminus of the NOVX polypeptide.

[0110] In one embodiment, the fusion protein is a GST-NOVX fusionprotein in which the NOVX sequences are fused to the C-terminus of theGST (glutathione S-transferase) sequences. Such fusion proteins canfacilitate the purification of recombinant NOVX polypeptides.

[0111] In another embodiment, the fusion protein is a NOVX proteincontaining a heterologous signal sequence at its N-terminus. In certainhost cells (e.g., mammalian host cells), expression and/or secretion ofNOVX can be increased through use of a heterologous signal sequence.

[0112] In yet another embodiment, the fusion protein is aNOVX-immunoglobulin fusion protein in which the NOVX sequences are fusedto sequences derived from a member of the immunoglobulin protein family.The NOVX-immunoglobulin fusion proteins of the invention can beincorporated into pharmaceutical compositions and administered to asubject to inhibit an interaction between a NOVX ligand and a NOVXprotein on the surface of a cell, to thereby suppress NOVX-mediatedsignal transduction in vivo. The NOVX-immunoglobulin fusion proteins canbe used to affect the bioavailability of a NOVX cognate ligand.Inhibition of the NOVX ligand/NOVX interaction may be usefultherapeutically for both the treatment of proliferative anddifferentiative disorders, as well as modulating (e.g. promoting orinhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusionproteins of the invention can be used as immunogens to produce anti-NOVXantibodies in a subject, to purify NOVX ligands, and in screening assaysto identify molecules that inhibit the interaction of NOVX with a NOVXligand.

[0113] A NOVX chimeric or fusion protein of the invention can beproduced by standard recombinant DNA techniques. For example, DNAfragments coding for the different polypeptide sequences are ligatedtogether in-frame in accordance with conventional techniques, e.g. byemploying blunt-ended or stagger-ended termini for ligation, restrictionenzyme digestion to provide for appropriate termini, filling-in ofcohesive ends as appropriate, alkaline phosphatase treatment to avoidundesirable joining, and enzymatic ligation. In another embodiment, thefusion gene can be synthesized by conventional techniques includingautomated DNA synthesizers. Alternatively, PCR amplification of genefragments can be carried out using anchor primers that give rise tocomplementary overhangs between two consecutive gene fragments that cansubsequently be annealed and reamplified to generate a chimeric genesequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS INMOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expressionvectors are commercially available that already encode a fusion moiety(e.g., a GST polypeptide). A NOVX-encoding nucleic acid can be clonedinto such an expression vector such that the fusion moiety is linkedin-frame to the NOVX protein.

[0114] NOVX Agonists and Antagonists

[0115] The invention also pertains to variants of the NOVX proteins thatfunction as either NOVX agonists (i.e. mimetics) or as NOVX antagonists.Variants of the NOVX protein can be generated by mutagenesis (e.g.discrete point mutation or truncation of the NOVX protein). An agonistof the NOVX protein can retain substantially the same, or a subset ofthe biological activities of the naturally occurring form of the NOVXprotein. An antagonist of the NOVX protein can inhibit one or more ofthe activities of the naturally occurring form of the NOVX protein by,for example, competitively binding to a downstream or upstream member ofa cellular signaling cascade which includes the NOVX protein. Thus,specific biological effects can be elicited by treatment with a variantof limited function. In one embodiment, treatment of a subject with avariant having a subset of the biological activities of the naturallyoccurring form of the protein has fewer side effects in a subjectrelative to treatment with the naturally occurring form of the NOVXproteins.

[0116] Variants of the NOVX proteins that function as either NOVXagonists (i.e. mimetics) or as NOVX antagonists can be identified byscreening combinatorial libraries of mutants (e.g. truncation mutants)of the NOVX proteins for NOVX protein agonist or antagonist activity. Inone embodiment, a variegated library of NOVX variants is generated bycombinatorial mutagenesis at the nucleic acid level and is encoded by avariegated gene library. A variegated library of NOVX variants can beproduced by, for example, enzymatically ligating a mixture of syntheticoligonucleotides into gene sequences such that a degenerate set ofpotential NOVX sequences is expressible as individual polypeptides, oralternatively, as a set of larger fusion proteins (e.g., for phagedisplay) containing the set of NOVX sequences therein. There are avariety of methods which can be used to produce libraries of potentialNOVX variants from a degenerate oligonucleotide sequence. Chemicalsynthesis of a degenerate gene sequence can be performed in an automaticDNA synthesizer, and the synthetic gene then ligated into an appropriateexpression vector. Use of a degenerate set of genes allows for theprovision, in one mixture, of all of the sequences encoding the desiredset of potential NOVX sequences. Methods for synthesizing degenerateoligonucleotides are well-known within the art. See, e.g., Narang, 1983,Tetrahedron 39: 3; Itakura, et al., 1984, Annu. Rev Biochem 53: 323;Itakura, et al., 1984, Science 198: 1056; Ike, et al., 1983, Nucl AcidsRes 11: 477.

[0117] Polypeptide Libraries

[0118] In addition, libraries of fragments of the NOVX protein codingsequences can be used to generate a variegated population of NOVXfragments for screening and subsequent selection of variants of a NOVXprotein. In one embodiment, a library of coding sequence fragments canbe generated by treating a double stranded PCR fragment of a NOVX codingsequence with a nuclease under conditions wherein nicking occurs onlyabout once per molecule, denaturing the double stranded DNA, renaturingthe DNA to form double-stranded DNA that can include sense/antisensepairs from different nicked products, removing single stranded portionsfrom reformed duplexes by treatment with S₁ nuclease, and ligating theresulting fragment library into an expression vector. By this method,expression libraries can be derived which encodes N-terminal andinternal fragments of various sizes of the NOVX proteins.

[0119] Various techniques are known in the art for screening geneproducts of combinatorial libraries made by point mutations ortruncation, and for screening cDNA libraries for gene products having aselected property. Such techniques are adaptable for rapid screening ofthe gene libraries generated by the combinatorial mutagenesis of NOVXproteins. The most widely used techniques, which are amenable to highthroughput analysis, for screening large gene libraries typicallyinclude cloning the gene library into replicable expression vectors,transforming appropriate cells with the resulting library of vectors,and expressing the combinatorial genes under conditions in whichdetection of a desired activity facilitates isolation of the vectorencoding the gene whose product was detected. Recursive ensemblemutagenesis (REM), a new technique that enhances the frequency offunctional mutants in the libraries, can be used in combination with thescreening assays to identify NOVX variants. See, e.g., Arkin andYourvan, 1992, Proc Natl Acad Sci USA 89: 7811-7815; Delgrave, et al.,1993, Protein Engineering 6:327-331.

[0120] Anti-NOVX Antibodies

[0121] Included in the invention are antibodies to NOVX proteins, orfragments of NOVX proteins. The term “antibody” as used herein refers toimmunoglobulin molecules and immunologically active portions ofimmunoglobulin (Ig) molecules, i.e. molecules that contain an antigenbinding site that specifically binds (immunoreacts with) an antigen.Such antibodies include, but are not limited to, polyclonal, monoclonal,chimeric, single chain, F_(ab), F_(ab) and F_((ab′)2) fragments, and anF_(ab) expression library. In general, antibody molecules obtained fromhumans relates to any of the classes IgG, IgM, IgA, IgE and IgD, whichdiffer from one another by the nature of the heavy chain present in themolecule. Certain classes have subclasses as well, such as IgG₁, IgG₂,and others. Furthermore, in humans, the light chain may be a kappa chainor a lambda chain. Reference herein to antibodies includes a referenceto all such classes, subclasses and types of human antibody species.

[0122] An isolated protein of the invention intended to serve as anantigen, or a portion or fragment thereof, can be used as an immunogento generate antibodies that immunospecifically bind the antigen, usingstandard techniques for polyclonal and monoclonal antibody preparation.The full-length protein can be used or, alternatively, the inventionprovides antigenic peptide fragments of the antigen for use asimmunogens. An antigenic peptide fragment comprises at least 6 aminoacid residues of the amino acid sequence of the full length protein,such as an amino acid sequence of SEQ ID NO:2n, wherein n is an integerbetween 1 and 44, and encompasses an epitope thereof such that anantibody raised against the peptide forms a specific immune complex withthe full length protein or with any fragment that contains the epitope.Preferably, the antigenic peptide comprises at least 10 amino acidresidues, or at least 15 amino acid residues, or at least 20 amino acidresidues, or at least 30 amino acid residues. Preferred epitopesencompassed by the antigenic peptide are regions of the protein that arelocated on its surface; commonly these are hydrophilic regions.

[0123] In certain embodiments of the invention, at least one epitopeencompassed by the antigenic peptide is a region of NOVX that is locatedon the surface of the protein, e.g. a hydrophilic region. Ahydrophobicity analysis of the human NOVX protein sequence will indicatewhich regions of a NOVX polypeptide are particularly hydrophilic and,therefore, are likely to encode surface residues useful for targetingantibody production. As a means for targeting antibody production,hydropathy plots showing regions of hydrophilicity and hydrophobicitymay be generated by any method well known in the art, including, forexample, the Kyte Doolittle or the Hopp Woods methods, either with orwithout Fourier transformation. See, e.g. Hopp and Woods, 1981, Proc.Natl Acad. Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J Mol Biol.157: 105-142, each incorporated herein by reference in their entirety.Antibodies that are specific for one or more domains within an antigenicprotein or derivatives, fragments, analogs or homologs thereof, are alsoprovided herein.

[0124] The tern “epitope” includes any protein determinant capable ofspecific binding to an immunoglobulin or T-cell receptor. Epitopicdeterminants usually consist of chemically active surface groupings ofmolecules such as amino acids or sugar side chains and usually havespecific three dimensional structural characteristics, as well asspecific charge characteristics. A NOVX polypeptide or a fragmentthereof comprises at least one antigenic epitope. An anti-NOVX antibodyof the present invention is said to specifically bind to antigen NOVXwhen the equilibrium binding constant (K_(D)) is ≦1 μM, preferably ≦100nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM,as measured by assays such as radioligand binding assays or similarassays known to those skilled in the art.

[0125] A protein of the invention, or a derivative, fragment, analog,homolog or ortholog thereof, may be utilized as an immunogen in thegeneration of antibodies that immunospecifically bind these proteincomponents.

[0126] Various procedures known within the art may be used for theproduction of polyclonal or monoclonal antibodies directed against aprotein of the invention, or against derivatives, fragments, analogshomologs or orthologs thereof (see, for example, Antibodies: ALaboratory Manual, Harlow E. and Lane D. 1988, Cold Spring HarborLaboratory Press, Cold Spring Harbor, N.Y., incorporated herein byreference). Some of these antibodies are discussed below.

[0127] Polyclonal-Antibodies

[0128] For the production of polyclonal antibodies, various suitablehost animals (e.g. rabbit, goat, mouse or other mammal) may be immunizedby one or more injections with the native protein, a synthetic variantthereof, or a derivative of the foregoing. An appropriate immunogenicpreparation can contain, for example, the naturally occurringimmunogenic protein, a chemically synthesized polypeptide representingthe immunogenic protein, or a recombinantly expressed immunogenicprotein. Furthermore, the protein may be conjugated to a second proteinknown to be immunogenic in the mammal being immunized. Examples of suchimmunogenic proteins include but are not limited to keyhole limpethemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsininhibitor. The preparation can further include an adjuvant. Variousadjuvants used to increase the immunological response include, but arenot limited to, Freund's (complete and incomplete), mineral gels (e.g.,aluminum hydroxide), surface active substances (e.g., lysolecithin,pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol,etc.), adjuvants usable in humans such as Bacille Calmette-Guerin andCorynebacterium parvum, or similar immunostimulatory agents. Additionalexamples of adjuvants which can be employed include MPL-TDM adjuvant(monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).

[0129] The polyclonal antibody molecules directed against theimmunogenic protein can be isolated from the mammal (e.g., from theblood) and further purified by well known techniques, such as affinitychromatography using protein A or protein G, which provide primarily theIgG fraction of immune serum. Subsequently, or alternatively, thespecific antigen which is the target of the immunoglobulin sought, or anepitope thereof, may be immobilized on a column to purify the immunespecific antibody by immunoaffinity chromatography. Purification ofimmunoglobulins is discussed, for example, by D. Wilkinson (TheScientist, published by The Scientist, Inc., Philadelphia, Pa., Vol. 14,No. 8 (Apr. 17, 2000), pp. 25-28).

[0130] Monoclonal Antibodies

[0131] The term “monoclonal antibody” (MAb) or “monoclonal antibodycomposition”, as used herein, refers to a population of antibodymolecules that contain only one molecular species of antibody moleculeconsisting of a unique light chain gene product and a unique heavy chaingene product. In particular, the complementarity determining regions(CDRs) of the monoclonal antibody are identical in all the molecules ofthe population. MAbs thus contain antigen binding site capable ofimmunoreacting with a particular epitope of the antigen characterized bya unique binding affinity for it.

[0132] Monoclonal antibodies can be prepared using hybridoma methods,such as those described by Kohler and Milstein, Nature, 256:495 (1975).In a hybridoma method, a mouse, hamster, or other appropriate hostanimal, is typically, immunized with an immunizing agent to elicitlymphocytes that produce or are capable of producing antibodies thatwill specifically bind to the immunizing agent. Alternatively, thelymphocytes can be immunized in vitro.

[0133] The immunizing agent will typically include the protein antigen,a fragment thereof or a fusion protein thereof. Generally, eitherperipheral blood lymphocytes are used if cells of human origin aredesired, or spleen cells or lymph node cells are used if non-humanmammalian sources are desired. The lymphocytes are then fused with animmortalized cell line using a suitable fusing agent, such aspolyethylene glycol, to form a hybridoma cell (Goding, MonoclonalAntibodies: Principles and Practice, Academic Press, (1986) pp. 59-103).Immortalized cell lines are usually transformed mammalian cells,particularly myeloma cells of rodent, bovine and human origin. Usually,rat or mouse myeloma cell lines are employed. The hybridoma cells can becultured in a suitable culture medium that preferably contains one ormore substances that inhibit the growth or survival of the unfused,immortalized cells. For example, if the parental cells lack the enzymehypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), theculture medium for the hybridomas typically will include hypoxanthine,aminopterin, and thymidine (“HAT medium”), which substances prevent thegrowth of HGPRT-deficient cells.

[0134] Preferred immortalized cell lines are those that fuseefficiently, support stable high level expression of antibody by theselected antibody-producing cells, and are sensitive to a medium such asHAT medium. More preferred immortalized cell lines are murine myelomalines, which can be obtained, for instance, from the Salk Institute CellDistribution Center, San Diego, Calif. and the American Type CultureCollection, Manassas, Va. Human myeloma and mouse-human heteromyelomacell lines also have been described for the production of humanmonoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur etal., Monoclonal Antibody Production Techniques and Applications, MarcelDekker, Inc., New York, (1987) pp .51-63).

[0135] The culture medium in which the hybridoma cells are cultured canthen be assayed for the presence of monoclonal antibodies directedagainst the antigen. Preferably, the binding specificity of monoclonalantibodies produced by the hybridoma cells is determined byimmunoprecipitation or by an in vitro binding assay, such asradioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA).Such techniques and assays are known in the art. The binding affinity ofthe monoclonal antibody can, for example, be determined by the Scatchardanalysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is anobjective, especially important in therapeutic applications ofmonoclonal antibodies, to identify antibodies having a high degree ofspecificity and a high binding affinity for the target antigen.

[0136] After the desired hybridoma cells are identified, the clones canbe subcloned by limiting dilution procedures and grown by standardmethods (Goding, 1986). Suitable culture media for this purpose include,for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium.Alternatively, the hybridoma cells can be grown in vivo as ascites in amammal.

[0137] The monoclonal antibodies secreted by the subclones can beisolated or purified from the culture medium or ascites fluid byconventional immunoglobulin purification procedures such as, forexample, protein A-Sepharose, hydroxylapatite chromatography, gelelectrophoresis, dialysis, or affinity chromatography.

[0138] The monoclonal antibodies can also be made by recombinant DNAmethods, such as those described in U.S. Pat. No. 4,816,567. DNAencoding the monoclonal antibodies of the invention can be readilyisolated and sequenced using conventional procedures (e.g. by usingoligonucleotide probes that are capable of binding specifically to genesencoding the heavy and light chains of murine antibodies). The hybridomacells of the invention serve as a preferred source of such DNA. Onceisolated, the DNA can be placed into expression vectors, which are thentransfected into host cells such as simian COS cells, Chinese hamsterovary (CHO) cells, or myeloma cells that do not otherwise produceimmunoglobulin protein, to obtain the synthesis of monoclonal antibodiesin the recombinant host cells. The DNA also can be modified, forexample, by substituting the coding sequence for human heavy and lightchain constant domains in place of the homologous murine sequences (U.S.Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or bycovalently joining to the immunoglobulin coding sequence all or part ofthe coding sequence for a non-immunoglobulin polypeptide. Such anon-immunoglobulin polypeptide can be substituted for the constantdomains of an antibody of the invention, or can be substituted for thevariable domains of one antigen-combining site of an antibody of theinvention to create a chimeric bivalent antibody

[0139] Humanized Antibodies

[0140] The antibodies directed against the protein antigens of theinvention can further comprise humanized antibodies or human antibodies.These antibodies are suitable for administration to humans withoutengendering an immune response by the human against the administeredimmunoglobulin. Humanized forms of antibodies are chimericimmunoglobulins, immunoglobulin chains or fragments thereof (such as Fv,Fab, Fab′, F(ab′)₂ or other antigen-binding subsequences of antibodies)that are principally comprised of the sequence of a humanimmunoglobulin, and contain minimal sequence derived from a non-humanimmunoglobulin. Humanization can be performed following the method ofWinter and co-workers (Jones et al., Nature, 321:522-525 (1986);Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science,239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences forthe corresponding sequences of a human antibody. (See also U.S. Pat. No.5,225,539.) In some instances, Fv framework residues of the humanimmunoglobulin are replaced by corresponding non-human residues.Humanized antibodies can also comprise residues which are found neitherin the recipient antibody nor in the imported CDR or frameworksequences. In general, the humanized antibody will comprisesubstantially all of at least one, and typically two, variable domains,in which all or substantially all of the CDR regions correspond to thoseof a non-human immunoglobulin and all or substantially all of theframework regions are those of a human immunoglobulin consensussequence. The humanized antibody optimally also will comprise at least aportion of an immunoglobulin constant region (Fc), typically that of ahuman immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; andPresta. Curr. Op. Struct. Biol., 2:593-596 (1992)).

[0141] Human Antibodies

[0142] Fully human antibodies essentially relate to antibody moleculesin which the entire sequence of both the light chain and the heavychain, including the CDRs, arise from human genes. Such antibodies aretermed “human antibodies”, or “fully human antibodies” herein. Humanmonoclonal antibodies can be prepared by the trioma technique; the humanB-cell hybridoma technique (See Kozbor, et al., 1983 Immunol Today 4:72) and the EBV hybridoma technique to produce human monoclonalantibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCERTHERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies maybe utilized in the practice of the present invention and may be producedby using human hybridomas (see Cote, et al., 1983, Proc Natl Acad SciUSA 80: 2026-2030) or by transforming human B-cells with Epstein BarrVirus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES ANDCANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).

[0143] In addition, human antibodies can also be produced usingadditional techniques, including phage display libraries (Hoogenboom andWinter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol.,222:581 (1991)). Similarly, human antibodies can be made by introducinghuman immunoglobulin loci into transgenic animals, e.g., mice in whichthe endogenous immunoglobulin genes have been partially or completelyinactivated. Upon challenge, human antibody production is observed,which closely resembles that seen in humans in all respects, includinggene rearrangement, assembly, and antibody repertoire. This approach isdescribed, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806;5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al.(Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859(1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild et al, (NatureBiotechnology 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14,826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93(1995)).

[0144] Human antibodies may additionally be produced using transgenicnonhuman animals which are modified so as to produce fully humanantibodies rather than the animal's endogenous antibodies in response tochallenge by an antigen. (See PCT publication WO94/02602). Theendogenous genes encoding the heavy and light immunoglobulin chains inthe nonhuman host have been incapacitated, and active loci encodinghuman heavy and light chain immunoglobulins are inserted into the host'sgenome. The human genes are incorporated, for example, using yeastartificial chromosomes containing the requisite human DNA segments. Ananimal which provides all the desired modifications is then obtained asprogeny by crossbreeding intermediate transgenic animals containingfewer than the full complement of the modifications. The preferredembodiment of such a nonhuman animal is a mouse, and is termed theXenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096.This animal produces B cells which secrete fully human immunoglobulins.The antibodies can be obtained directly from the animal afterimmunization with an immunogen of interest, as, for example, apreparation of a polyclonal antibody, or alternatively from immortalizedB cells derived from the animal, such as hybridomas producing monoclonalantibodies. Additionally, the genes encoding the immunoglobulin withhuman variable regions can be recovered and expressed to obtain theantibodies directly, or can be further modified to obtain analogs ofantibodies such as, for example, single chain Fv molecules.

[0145] An example of a method of producing a nonhuman host, exemplifiedas a mouse, lacking expression of an endogenous immunoglobulin heavychain is disclosed in U.S. Pat. No. 5,939,598. It can be obtained by amethod including deleting the J segment genes from at least oneendogenous heavy chain locus in an embryonic stem cell to preventrearrangement of the locus and to prevent formation of a transcript of arearranged immunoglobulin heavy chain locus, the deletion being effectedby a targeting vector containing a gene encoding a selectable marker;and producing from the embryonic stem cell a transgenic mouse whosesomatic and germ cells contain the gene encoding the selectable marker.

[0146] A method for producing an antibody of interest, such as a humanantibody, is disclosed in U.S. Pat. No. 5,916,771. It includesintroducing an expression vector that contains a nucleotide sequenceencoding a heavy chain into one mammalian host cell in culture,introducing an expression vector containing a nucleotide sequenceencoding a light chain into another mammalian host cell, and fusing thetwo cells to form a hybrid cell. The hybrid cell expresses an antibodycontaining the heavy chain and the light chain.

[0147] In a further improvement on this procedure, a method foridentifying a clinically relevant epitope on an immunogen, and acorrelative method for selecting an antibody that bindsimmunospecifically to the relevant epitope with high affinity, aredisclosed in PCT publication WO 99/53049.

[0148] F_(ab) Fragments and Single Chain Antibodies

[0149] According to the invention, techniques can be adapted for theproduction of single-chain antibodies specific to an antigenic proteinof the invention (see e.g. U.S. Pat. No. 4,946,778). In addition,methods can be adapted for the construction of F_(ab) expressionlibraries (see e.g. Huse, et al., 1989 Science 246: 1275-1281) to allowrapid and effective identification of monoclonal F_(ab) fragments withthe desired specificity for a protein or derivatives, fragments, analogsor homologs thereof. Antibody fragments that contain the idiotypes to aprotein antigen may be produced by techniques known in the artincluding, but not limited to: (i) an F_((ab′)2) fragment produced bypepsin digestion of an antibody molecule; (ii) an F_(ab) fragmentgenerated by reducing the disulfide bridges of an F_((ab′)2) fragment;(iii) an F_(ab) fragment generated by the treatment of the antibodymolecule with papain and a reducing agent and (iv) F_(v) fragments.

[0150] Bispecific Antibodies

[0151] Bispecific antibodies are monoclonal, preferably human orhumanized, antibodies that have binding specificities for at least twodifferent antigens. In the present case, one of the bindingspecificities is for an antigenic protein of the invention. The secondbinding target is any other antigen, and advantageously is acell-surface protein or receptor or receptor subunit.

[0152] Methods for making bispecific antibodies are known in the art.Traditionally, the recombinant production of bispecific antibodies isbased on the co-expression of two immunoglobulin heavy-chain/light-chainpairs, where the two heavy chains have different specificities (Milsteinand Cuello, Nature, 305:537-539 (1983)). Because of the randomassortment of immunoglobulin heavy and light chains, these hybridomas(quadromas) produce a potential mixture of ten different antibodymolecules, of which only one has the correct bispecific structure. Thepurification of the correct molecule is usually accomplished by affinitychromatography steps. Similar procedures are disclosed in WO 93/08829,published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659(1991).

[0153] Antibody variable domains with the desired binding specificities(antibody-antigen combining sites) can be fused to immunoglobulinconstant domain sequences. The fusion preferably is with animmunoglobulin heavy-chain constant domain, comprising at least part ofthe hinge, CH2, and CH3 regions. It is preferred to have the firstheavy-chain constant region (CH1) containing the site necessary forlight-chain binding present in at least one of the fusions. DNAsencoding the immunoglobulin heavy-chain fusions and, if desired, theimmunoglobulin light chain, are inserted into separate expressionvectors, and are co-transfected into a suitable host organism. Forfurther details of generating bispecific antibodies see, for example,Suresh et al., Methods in Enzymology, 121:210 (1986).

[0154] According to another approach described in WO 96/27011, theinterface between a pair of antibody molecules can be engineered tomaximize the percentage of heterodimers which are recovered fromrecombinant cell culture. The preferred interface comprises at least apart of the CH3 region of an antibody constant domain. In this method,one or more small amino acid side chains from the interface of the firstantibody molecule are replaced with larger side chains (e.g. tyrosine ortryptophan). Compensatory “cavities” of identical or similar size to thelarge side chain(s) are created on the interface of the second antibodymolecule by replacing large amino acid side chains with smaller ones(e.g. alanine or threonine). This provides a mechanism for increasingthe yield of the heterodimer over other unwanted end-products such ashomodimers.

[0155] Bispecific antibodies can be prepared as full length antibodiesor antibody fragments (e.g. F(ab′)₂ bispecific antibodies) Techniquesfor generating bispecific antibodies from antibody fragments have beendescribed in the literature. For example, bispecific antibodies can beprepared using chemical linkage. Brennan et al., Science 229:81 (1985)describe a procedure wherein intact antibodies are proteolyticallycleaved to generate F(ab′)₂ fragments. These fragments are reduced inthe presence of the dithiol complexing agent sodium arsenite tostabilize vicinal dithiols and prevent intermolecular disulfideformation. The Fab′ fragments generated are then converted tothionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives isthen reconverted to the Fab′-thiol by reduction with mercaptoethlylamineand is mixed with an equimolar amount of the other Fab′-TNB derivativeto form the bispecific antibody. The bispecific antibodies produced canbe used as agents for the selective immobilization of enzymes.

[0156] Additionally. Fab′ fragments can be directly recovered from E.coli and chemically coupled to form bispecific antibodies. Shalaby etal., J. Exp. Med. 175:217-225 (1992) describe the production of a fullyhumanized bispecific antibody F(ab′)₂ molecule. Each Fab′ fragment wasseparately secreted from E. coli and subjected to directed chemicalcoupling in vitro to form the bispecific antibody. The bispecificantibody thus formed was able to bind to cells overexpressing the ErbB2receptor and normal human T cells, as well as trigger the lytic activityof human cytotoxic lymphocytes against human breast tumor targets.

[0157] Various techniques for making and isolating bispecific antibodyfragments directly from recombinant cell culture have also beendescribed. For example, bispecific antibodies have been produced usingleucine zippers. Kostelny et al., J. Immunol. 148(5): 1547-1553 (1992).The leucine zipper peptides from the Fos and Jun proteins were linked tothe Fab′ portions of two different antibodies by gene fusion. Theantibody homodimers were reduced at the hinge region to form monomersand then re-oxidized to form the antibody heterodimers. This method canalso be utilized for the production of antibody homodimers. The“diabody” technology described by Hollinger et al., Proc. Natl. Acad.Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism formaking bispecific antibody fragments. The fragments comprise aheavy-chain variable domain (V_(H)) connected to a light-chain variabledomain (V_(L)) by a linker which is too short to allow pairing betweenthe two domains on the same chain. Accordingly, the V_(H) and V_(L)domains of one fragment are forced to pair with the complementary V_(L)and V_(H) domains of another fragment, thereby forming twoantigen-binding sites. Another strategy for making bispecific antibodyfragments by the use of single-chain Fv (sFv) dimers has also beenreported. See, Gruber et al., J. Immunol. 152:5368 (1994).

[0158] Antibodies with more than two valencies are contemplated. Forexample, trispecific antibodies can be prepared. Tutt et al., J.Immunol. 147:60 (1991).

[0159] Exemplary bispecific antibodies can bind to two differentepitopes, at least one of which originates in the protein antigen of theinvention. Alternatively, an anti-antigenic arm of an immunoglobulinmolecule can be combined with an arm which binds to a triggeringmolecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2,CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64),FcγRII (CD32) and FcγRIII (CD16) so as to focus cellular defensemechanisms to the cell expressing the particular antigen. Bispecificantibodies can also be used to direct cytotoxic agents to cells whichexpress a particular antigen. These antibodies possess anantigen-binding arm and an arm which binds a cytotoxic agent or aradionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Anotherbispecific antibody of interest binds the protein antigen describedherein and further binds tissue factor (TF).

[0160] Heteroconjugate Antibodies

[0161] Heteroconjugate antibodies are also within the scope of thepresent invention. Heteroconjugate antibodies are composed of twocovalently joined antibodies. Such antibodies have, for example, beenproposed to target immune system cells to unwanted cells (U.S. Pat. No.4,676,980), and for treatment of HIV infection (WO 91/00360; WO92/200373; EP 03089). It is contemplated that the antibodies can beprepared in vitro using known methods in synthetic protein chemistry,including those involving crosslinking agents. For example, immunotoxinscan be constructed using a disulfide exchange reaction or by forming athioether bond. Examples of suitable reagents for this purpose includeiminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, forexample, in U.S. Pat. No.4,676,980.

[0162] Effector Function Engineering

[0163] It can be desirable to modify the antibody of the invention withrespect to effector function, so as to enhance, e.g. the effectivenessof the antibody in treating cancer. For example, cysteine residue(s) canbe introduced into the Fc region, thereby allowing interchain disulfidebond formation in this region. The homodimeric antibody thus generatedcan have improved internalization capability and/or increasedcomplement-mediated cell killing and antibody-dependent cellularcytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 144-1195 (1992)and Shopes, J. Immunol., 148: 2918-2922 (1992). Homodimeric antibodieswith enhanced anti-tumor activity can also be prepared usingheterobifunctional cross-linkers as described in Wolff et al. CancerResearch, 53: 2560-2565 (1993). Alternatively, an antibody can beengineered that has dual Fc regions and can thereby have enhancedcomplement lysis and ADCC capabilities. See Stevenson et al.,Anti-Cancer Drug Design, 3: 219-230 (1989).

[0164] Immunoconjugates

[0165] The invention also pertains to immunoconjugates comprising anantibody conjugated to a cytotoxic agent such as a chemotherapeuticagent, toxin (e.g., an enzymatically active toxin of bacterial, fungal,plant, or animal origin, or fragments thereof), or a radioactive isotope(i.e., a radioconjugate).

[0166] Chemotherapeutic agents useful in the generation of suchimmunoconjugates have been described above. Enzymatically active toxinsand fragments thereof that can be used include diphtheria A chain,nonbinding active fragments of diphtheria toxin, exotoxin A chain (fromPseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain,alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolacaamericana proteins (PAPI, PAPII, and PAP-S), momordica charantiainhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin,mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. Avariety of radionuclides are available for the production ofradioconjugated antibodies. Examples include ²¹²Bi, ¹³¹I, ¹³¹In, ⁹⁰Y,and ¹⁸⁶Re.

[0167] Conjugates of the antibody and cytotoxic agent are made using avariety of bifunctional protein-coupling agents such asN-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane(IT), bifunctional derivatives of imidoesters (such as dimethyladipimidate HCL), active esters (such as disuccinimidyl suberate),aldehydes (such as glutareldehyde), bis-azido compounds (such asbis(p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such asbis-(p-diazoniumbenzoyl)ethylenediamine), diisocyanates (such as tolyene2,6-diisocyanate), and bis-active fluorine compounds (such as1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin canbe prepared as described in Vitetta et al., Science, 238: 1098 (1987).Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylenetriaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent forconjugation of radionucleotide to the antibody. See WO94/11026.

[0168] In another embodiment, the antibody can be conjugated to a“receptor” (such streptavidin) for utilization in tumor pretargetingwherein the antibody-receptor conjugate is administered to the patient,followed by removal of unbound conjugate from the circulation using aclearing agent and then administration of a “ligand” (e.g., avidin) thatis in turn conjugated to a cytotoxic agent.

[0169] Immunoliposomes

[0170] The antibodies disclosed herein can also be formulated asimmunoliposomes. Liposomes containing the antibody are prepared bymethods known in the art, such as described in Epstein et al., Proc.Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad.Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545.Liposomes with enhanced circulation time are disclosed in U.S. Pat. No.5,013,556.

[0171] Particularly useful liposomes can be generated by thereverse-phase evaporation method with a lipid composition comprisingphosphatidylcholine, cholesterol, and PEG-derivatizedphosphatidylethanolamine (PEG-PE). Liposomes are extruded throughfilters of defined pore size to yield liposomes with the desireddiameter. Fab′ fragments of the antibody of the present invention can beconjugated to the liposomes as described in Martin et al., J. Biol.Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. Achemotherapeutic agent (such as Doxorubicin) is optionally containedwithin the liposome. See Gabizon et al., J. National Cancer Inst.,81(19): 1484 (1989).

[0172] Diagnostic Applications of Antibodies Directed Against theProteins of the Invention

[0173] In one embodiment, methods for the screening of antibodies thatpossess the desired specificity include, but are not limited to, enzymelinked immunosorbent assay (ELISA) and other immunologically mediatedtechniques known within the art. In a specific embodiment, selection ofantibodies that are specific to a particular domain of an NOVX proteinis facilitated by generation of hybridomas that bind to the fragment ofan NOVX protein possessing such a domain. Thus, antibodies that arespecific for a desired domain within an NOVX protein, or derivatives,fragments, analogs or homologs thereof, are also provided herein.

[0174] Antibodies directed against a NOVX protein of the invention maybe used in methods known within the art relating to the localizationand/or quantitation of a NOVX protein (e.g., for use in measuring levelsof the NOVX protein within appropriate physiological samples, for use indiagnostic methods, for use in imaging the protein, and the like). In agiven embodiment, antibodies specific to a NOVX protein, or derivative,fragment, analog or homolog thereof, that contain the antibody derivedantigen binding domain, are utilized as pharmacologically activecompounds (referred to hereinafter as “Therapeutics”).

[0175] An antibody specific for a NOVX protein of the invention (e.g., amonoclonal antibody or a polyclonal antibody) can be used to isolate aNOVX polypeptide by standard techniques, such as immunoaffinity,chromatography or immunoprecipitation. An antibody to a NOVX polypeptidecan facilitate the purification of a natural NOVX antigen from cells, orof a recombinantly produced NOVX antigen expressed in host cells.Moreover, such an anti-NOVX antibody can be used to detect the antigenicNOVX protein (e.g., in a cellular lysate or cell supernatant) in orderto evaluate the abundance and pattern of expression of the antigenicNOVX protein. Antibodies directed against a NOVX protein can be useddiagnostically to monitor protein levels in tissue as part of a clinicaltesting procedure, e.g., to, for example, determine the efficacy of agiven treatment regimen. Detection can be facilitated by coupling,(i.e., physically linking) the antibody to a detectable substance.Examples of detectable substances include various enzymes, prostheticgroups, fluorescent materials, luminescent materials, bioluminescentmaterials, and radioactive materials. Examples of suitable enzymesinclude horseradish peroxidase, alkaline phosphatase, -galactosidase, oracetylcholinesterase; examples of suitable prosthetic group complexesinclude streptavidin/biotin and avidin/biotin; examples of suitablefluorescent materials include umbelliferone, fluorescein, fluoresceinisothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansylchloride or phycoerythrin; an example of a luminescent material includesluminol; examples of bioluminescent materials include luciferase,luciferin, and aequorin, and examples of suitable radioactive materialinclude ¹²⁵I, ¹³¹I, ³⁵S or ³H.

[0176] Antibody Therapeutics

[0177] Antibodies of the invention, including polyclonal, monoclonal,humanized and fully human antibodies, may used as therapeutic agents.Such agents will generally be employed to treat or prevent a disease orpathology in a subject. An antibody preparation, preferably one havinghigh specificity and high affinity for its target antigen, isadministered to the subject and will generally have an effect due to itsbinding with the target. Such an effect may be one of two kinds,depending on the specific nature of the interaction between the givenantibody molecule and the target antigen in question. In the firstinstance, administration of the antibody may abrogate or inhibit thebinding of the target with an endogenous ligand to which it naturallybinds. In this case, the antibody binds to the target and masks abinding site of the naturally occurring ligand, wherein the ligandserves as an effector molecule. Thus the receptor mediates a signaltransduction pathway for which ligand is responsible.

[0178] Alternatively, the effect may be one in which the antibodyelicits a physiological result by virtue of binding to an effectorbinding site on the target molecule. In this case the target, a receptorhaving an endogenous ligand which may be absent or defective in thedisease or pathology, binds the antibody as a surrogate effector ligand,initiating a receptor-based signal transduction event by the receptor.

[0179] A therapeutically effective amount of an antibody of theinvention relates generally to the amount needed to achieve atherapeutic objective. As noted above, this may be a binding interactionbetween the antibody and its target antigen that, in certain cases,interferes with the functioning of the target, and in other cases,promotes a physiological response. The amount required to beadministered will furthermore depend on the binding affinity of theantibody for its specific antigen, and will also depend on the rate atwhich an administered antibody is depleted from the free volume othersubject to which it is administered. Common ranges for therapeuticallyeffective dosing of an antibody or antibody fragment of the inventionmay be, by way of nonlimiting example, from about 0.1 mg/kg body weightto about 50 mg/kg body weight. Common dosing frequencies may range, forexample, from twice daily to once a week.

[0180] Pharmaceutical Compositions of Antibodies

[0181] Antibodies specifically binding a protein of the invention, aswell as other molecules identified by the screening assays disclosedherein, can be administered for the treatment of various disorders inthe form of pharmaceutical compositions. Principles and considerationsinvolved in preparing such compositions, as well as guidance in thechoice of components are provided, for example, in Remington: TheScience And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al.,editors) Mack Pub. Co., Easton, Pa.; 1995; Drug Absorption Enhancement:Concepts, Possibilities, Limitations, And Trends. Harwood AcademicPublishers, Langhorne. Pa., 1994; and Peptide And Protein Drug Delivery(Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.

[0182] If the antigenic protein is intracellular and whole antibodiesare used as inhibitors, internalizing, antibodies are preferred.However, liposomes can also be used to deliver the antibody, or anantibody fragment, into cells. Where antibody fragments are used, thesmallest inhibitory fragment that specifically binds to the bindingdomain of the target protein is preferred. For example, based upon thevariable-region sequences of an antibody, peptide molecules can bedesigned that retain the ability to bind the target protein sequence.Such peptides can be synthesized chemically and/or produced byrecombinant DNA technology. See, e.g. Marasco et al., Proc. Natl. Acad.Sci. USA. 90: 7889-7893 (1993). The formulation herein can also containmore than one active compound as necessary for the particular indicationbeing treated, preferably those with complementary activities that donot adversely affect each other. Alternatively, or in addition, thecomposition can comprise an agent that enhances its function, such as,for example, a cytotoxic agent, cytokine, chemotherapeutic agent, orgrowth-inhibitory agent. Such molecules are suitably present incombination in amounts that are effective for the purpose intended.

[0183] The active ingredients can also be entrapped in microcapsulesprepared, for example, by coacervation techniques or by interfacialpolymerization, for example, hydroxymethylcellulose orgelatin-microcapsules and poly-(methylmethacrylate) microcapsules,respectively, in colloidal drug delivery systems (for example,liposomes, albumin microspheres, microemulsions, nano-particles, andnanocapsules) or in macroemulsions.

[0184] The formulations to be used for in vivo administration must besterile. This is readily accomplished by filtration through sterilefiltration membranes.

[0185] Sustained-release preparations can be prepared. Suitable examplesof sustained-release preparations include semipermeable matrices ofsolid hydrophobic polymers containing the antibody, which matrices arein the form of shaped articles, e.g., films, or microcapsules. Examplesof sustained-release matrices include polyesters, hydrogels (forexample, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)),polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acidand γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate,degradable lactic acid-glycolic acid copolymers such as the LUPRONDEPOT™ (injectable microspheres composed of lactic acid-glycolic acidcopolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid.While polymers such as ethylene-vinyl acetate and lactic acid-glycolicacid enable release of molecules for over 100 days, certain hydrogelsrelease proteins for shorter time periods.

[0186] ELISA Assay

[0187] An agent for detecting an analyte protein is an antibody capableof binding to an analyte protein, preferably an antibody with adetectable label. Antibodies can be polyclonal, or more preferably,monoclonal. An intact antibody, or a fragment thereof (e.g., F_(ab) orF_((ab)2)) can be used. The term “labeled”, with regard to the probe orantibody, is intended to encompass direct labeling of the probe orantibody by coupling (i.e., physically linking) a detectable substanceto the probe or antibody, as well as indirect labeling of the probe orantibody by reactivity with another reagent that is directly labeled.Examples of indirect labeling include detection of a primary antibodyusing a fluorescently-labeled secondary antibody and end-labeling of aDNA probe with biotin such that it can be detected withfluorescently-labeled streptavidin. The term “biological sample” isintended to include tissues, cells and biological fluids isolated from asubject, as well as tissues, cells and fluids present within a subject.Included within the usage of the term “biological sample”, therefore, isblood and a fraction or component of blood including blood serum, bloodplasma, or lymph. That is, the detection method of the invention can beused to detect an analyte mRNA, protein, or genomic DNA in a biologicalsample in vitro as well as in vivo. For example, in vitro techniques fordetection of an analyte mRNA include Northern hybridizations and in situhybridizations. In vitro techniques for detection of an analyte proteininclude enzyme linked immunosorbent assays (ELISAs), Western blots,immunoprecipitations, and immunofluorescence. In vitro techniques fordetection of an analyte genomic DNA include Southern hybridizations.Procedures for conducting immunoassays are described, for example in“ELISA: Theory and Practice; Methods in Molecular Biology”, Vol. 42, J.R. Crowther (Ed.) Human Press, Totowa, N.J. 1995; “Immunoassay”, E.Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif.1996; and “Practice and Thory of Enzyme Immunoassays”, P. Tijssen,Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivotechniques for detection of an analyte protein include introducing intoa subject a labeled anti-an analyte protein antibody. For example, theantibody can be labeled with a radioactive marker whose presence andlocation in a subject can be detected by standard imaging techniques.

[0188] NOVX Recombinant Expression Vectors and Host Cells

[0189] Another aspect of the invention pertains to vectors, preferablyexpression vectors, containing a nucleic acid encoding a NOVX protein,or derivatives, fragments, analogs or homologs thereof. As used herein,the term “vector” refers to a nucleic acid molecule capable oftransporting another nucleic acid to which it has been linked. One typeof vector is a “plasmid”, which refers to a circular double stranded DNAloop into which additional DNA segments can be ligated. Another type ofvector is a viral vector, wherein additional DNA segments can be ligatedinto the viral genome. Certain vectors are capable of autonomousreplication in a host cell into which they are introduced (e.g.bacterial vectors having a bacterial origin of replication and episomalmammalian vectors). Other vectors (e.g. non-episomal mammalian vectors)are integrated into the genome of a host cell upon introduction into thehost cell, and thereby are replicated along with the host genome.Moreover, certain vectors are capable of directing the expression ofgenes to which they are operatively-linked. Such vectors are referred toherein as “expression vectors”. In general, expression vectors ofutility in recombinant DNA techniques are often in the form of plasmids.In the present specification, “plasmid” and “vector” can be usedinterchangeably as the plasmid is the most commonly used form of vector.However, the invention is intended to include such other forms ofexpression vectors, such as viral vectors (e.g. replication defectiveretroviruses, adenoviruses and adeno-associated viruses), which serveequivalent functions.

[0190] The recombinant expression vectors of the invention comprise anucleic acid of the invention in a form suitable for expression of thenucleic acid in a host cell, which means that the recombinant expressionvectors include one or more regulatory sequences, selected on the basisof the host cells to be used for expression, that is operatively-linkedto the nucleic acid sequence to be expressed. Within a recombinantexpression vector, “operably-linked” is intended to mean that thenucleotide sequence of interest is linked to the regulatory sequences(s)in a manner that allows for expression of the nucleotide sequence (e.g.in an in vitro transcription/translation system or in a host cell whenthe vector is introduced into the host cell).

[0191] The term “regulatory sequence” is intended to includes promoters,enhancers and other expression control elements (e.g. polyadenylationsignals). Such regulatory sequences are described, for example, inGoeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, AcademicPress, San Diego, Calif. (1990). Regulatory sequences include those thatdirect constitutive expression of a nucleotide sequence in many types ofhost cell and those that direct expression of the nucleotide sequenceonly in certain host cells (e.g., tissue-specific regulatory sequences).It will be appreciated by those skilled in the art that the design ofthe expression vector can depend on such factors as the choice of thehost cell to be transformed, the level of expression of protein desired,etc. The expression vectors of the invention can be introduced into hostcells to thereby produce proteins or peptides, including fusion proteinsor peptides, encoded by nucleic acids as described herein (e.g. NOVXproteins, mutant forms of NOVX proteins, fusion proteins, etc).

[0192] The recombinant expression vectors of the invention can bedesigned for expression of NOVX proteins in prokaryotic or eukaryoticcells. For example, NOVX proteins can be expressed in bacterial cellssuch as Escherichia coli, insect cells (using baculovirus expressionvectors) yeast cells or mammalian cells. Suitable host cells arediscussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS INENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Alternatively,the recombinant expression vector can be transcribed and translated invitro, for example using T7 promoter regulatory sequences and T7polymerase.

[0193] Expression of proteins in prokaryotes is most often carried outin Escherichia coli with vectors containing constitutive or induciblepromoters directing the expression of either fusion or non-fusionproteins. Fusion vectors add a number of amino acids to a proteinencoded therein, usually to the amino terminus of the recombinantprotein. Such fusion vectors typically serve three purposes: (i) toincrease expression of recombinant protein; (ii) to increase thesolubility of the recombinant protein; and (iii) to aid in thepurification of the recombinant protein by acting as a ligand inaffinity purification. Often, in fusion expression vectors, aproteolytic cleavage site is introduced at the junction of the fusionmoiety and the recombinant protein to enable separation of therecombinant protein from the fusion moiety subsequent to purification ofthe fusion protein. Such enzymes, and their cognate recognitionsequences, include Factor Xa, thrombin and enterokinase. Typical fusionexpression vectors include pGEX (Pharmacia Biotech Inc; Smith andJohnson, 1988, Gene 67: 31-40), pMAL (New England Biolabs, Beverly,Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathioneS-transferase (GST), maltose E binding protein, or protein A,respectively, to the target recombinant protein.

[0194] Examples of suitable inducible non-fusion E. coli expressionvectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET 11d(Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185,Academic Press, San Diego, Calif. (1990) 60-89).

[0195] One strategy to maximize recombinant protein expression in E.coli is to express the protein in a host bacteria with an impairedcapacity to proteolytically cleave the recombinant protein. See, e.g.,Gottesman, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185,Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is toalter the nucleic acid sequence of the nucleic acid to be inserted intoan expression vector so that the individual codons for each amino acidare those preferentially utilized in E. coli (see, e.g., Wada, et al.,1992, Nucl. Acids Res. 20: 2111-2118). Such alteration of nucleic acidsequences of the invention can be carried out by standard DNA synthesistechniques.

[0196] In another embodiment, the NOVX expression vector is a yeastexpression vector. Examples of vectors for expression in yeastSaccharomyces cerivisae include pYepSec1 (Baldari, et al., 1987, EMBO J.6: 229-234), pMFa (Kurjan and Herskowitz, 1982, Cell 30: 933-943),pJRY88 (Schultz et al., 1987, Gene 54: 113-123), pYES2 (Invitrogen(Corporation, San Diego, Calif.), and picZ (InVitrogen Corp. San Diego,Calif.).

[0197] Alternatively, NOVX can be expressed in insect cells usingbaculovirus expression vectors. Baculovirus vectors available forexpression of proteins in cultured insect cells (e.g. SF9 cells) includethe pAc series (Smith, et al., 1983, Mol. Cell. Biol 3: 2156-2165) andthe pVL series (Lucklow and Summers, 1989, Virology 170: 31-39).

[0198] In yet another embodiment, a nucleic acid of the invention isexpressed in mammalian cells using mammalian expression vector. Examplesof mammalian expression vectors include pCDM8 (Seed, 1987, Nature 329:840) and pMT2PC (Kaufman, et al., 1987, EMBO J. 6: 187-195). When usedin mammalian cells, the expression vector's control functions are oftenprovided by viral regulatory elements. For example, commonly usedpromoters are derived from polyoma, adenovirus 2, cytomegalovirus, andsimian virus 40. For other suitable expression systems for bothprokaryotic and eukaryotic cells see, e.g. Chapters 16 and 17 Sambrook,et al., MOLECULAR CLONING: A LABORATORY MANUAL, 2nd ed., Cold SpringHarbor Laboratory, Cold Spring Harbor Laboratory Press, Cold SpringHarbor, N.Y., 1989.

[0199] In another embodiment, the recombinant mammalian expressionvector is capable of directing expression of the nucleic acidpreferentially in a particular cell type (e.g., tissue-specificregulatory elements are used to express the nucleic acid).Tissue-specific regulatory elements are known in the art. Non-limitingexamples of suitable tissue-specific promoters include the albuminpromoter (liver-specific; Pinkert, et al., 1987, Genes Dev 1: 268-277),lymphoid-specific promoters (Calame and Eaton, 1988, Adv. Immunol. 43:235-275), in particular promoters of T cell receptors (Winoto andBaltimore, 1989, EMBO J. 8: 729-733) and immunoglobulins (Banerji, etal., 1983, Cell 33: 729-740; Queen and Baltimore, 1983, Cell 33:741-748), neuron-specific promoters (e.g., the neurofilament promoter;Byrne and Ruddle, 1989, Proc. Natl. Acad. Sci. USA 86: 5473-5477),pancreas-specific promoters (Edlund, et al., 1985, Science 230:912-916), and mammary gland-specific promoters (e.g., milk wheypromoter; U.S. Pat. No. 4,873,316 and European Application PublicationNo. 264,166). Developmentally-regulated promoters are also encompassed,e.g., the murine hox promoters (Kessel and Gruss, 1990, Science 249:374-379) and the -fetoprotein promoter (Campes and Tilghman, 1989, GenesDev 3: 537-546).

[0200] The invention further provides a recombinant expression vectorcomprising a DNA molecule of the invention cloned into the expressionvector in an antisense orientation. That is, the DNA molecule isoperatively-linked to a regulatory sequence in a manner that allows forexpression (by transcription of the DNA molecule) of an RNA moleculethat is antisense to NOVX mRNA. Regulatory sequences operatively linkedto a nucleic acid cloned in the antisense orientation can be chosen thatdirect the continuous expression of the antisense RNA molecule in avariety of cell types, for instance viral promoters and/or enhancers, orregulatory sequences can be chosen that direct constitutive, tissuespecific or cell type specific expression of antisense RNA. Theantisense expression vector can be in the form of a recombinant plasmid,phagemid or attenuated virus in which antisense nucleic acids areproduced under the control of a high efficiency regulatory region, theactivity of which can be determined by the cell type into which thevector is introduced. For a discussion of the regulation of geneexpression using antisense genes see e.g. Weintraub, et al., “AntisenseRNA as a molecular tool for genetic analysis,” Reviews—Trends inGenetics, Vol. 1(1) 1986.

[0201] Another aspect of the invention pertains to host cells into whicha recombinant expression vector of the invention has been introduced.The terms “host cell” and “recombinant host cell” are usedinterchangeably herein. It is understood that such terms refer not onlyto the particular subject cell but also to the progeny or potentialprogeny of such a cell. Because certain modifications may occur insucceeding generations due to either mutation or environmentalinfluences, such progeny may not, in fact, be identical to the parentcell, but are still included within the scope of the term as usedherein.

[0202] A host cell can be any prokaryotic or eukaryotic cell. Forexample, NOVX protein can be expressed in bacterial cells such as Ecoli, insect cells, yeast or mammalian cells (such as Chinese hamsterovary cells (CHO) or COS cells). Other suitable host cells are known tothose skilled in the art.

[0203] Vector DNA can be introduced into prokaryotic or eukaryotic cellsvia conventional transformation or transfection techniques. As usedherein, the terms “transformation” and “transfection” are intended torefer to a variety of art-recognized techniques for introducing foreignnucleic acid (e.g. DNA) into a host cell, including calcium phosphate orcalcium chloride co-precipitation. DEAE-dextran-mediated transfection,lipofection, or electroporation. Suitable methods for transforming ortransfecting host cells can be found in Sambrook, et al. (MOLECULARCLONING: A LABORATORY MANUAL, 2nd ed., Cold Spring Harbor Laboratory,Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989),and other laboratory manuals.

[0204] For stable transfection of mammalian cells, it is known that,depending upon the expression vector and transfection technique used,only a small fraction of cells may integrate the foreign DNA into theirgenome. In order to identify and select these integrants, a gene thatencodes a selectable marker (e.g. resistance to antibiotics) isgenerally introduced into the host cells along with the gene ofinterest. Various selectable markers include those that conferresistance to drugs, such as G418, hygromycin and methotrexate. Nucleicacid encoding a selectable marker can be introduced into a host cell onthe same vector as that encoding NOVX or can be introduced on a separatevector. Cells stably transfected with the introduced nucleic acid can beidentified by drug selection (e.g. cells that have incorporated theselectable marker gene will survive, while the other cells die).

[0205] A host cell of the invention, such as a prokaryotic or eukaryotichost cell in culture, can be used to produce (i.e., express) NOVXprotein. Accordingly, the invention further provides methods forproducing NOVX protein using the host cells of the invention. In oneembodiment, the method comprises culturing the host cell of invention(into which a recombinant expression vector encoding NOVX protein hasbeen introduced) in a suitable medium such that NOVX protein isproduced. In another embodiment, the method further comprises isolatingNOVX protein from the medium or the host cell.

[0206] Transgenic NOVX Animals

[0207] The host cells of the invention can also be used to producenon-human transgenic animals. For example, in one embodiment, a hostcell of the invention is a fertilized oocyte or an embryonic stem cellinto which NOVX protein-coding sequences have been introduced. Such hostcells can then be used to create non-human transgenic animals in whichexogenous NOVX sequences have been introduced into their genome orhomologous recombinant animals in which endogenous NOVX sequences havebeen altered. Such animals are useful for studying the function and/oractivity of NOVX protein and for identifying and/or evaluatingmodulators of NOVX protein activity. As used herein, a “transgenicanimal” is a non-human animal, preferably a mammal, more preferably arodent such as a rat or mouse, in which one or more of the cells of theanimal includes a transgene. Other examples of transgenic animalsinclude non-human primates, sheep, dogs, cows, goats, chickens,amphibians, etc. A transgene is exogenous DNA that is integrated intothe genome of a cell from which a transgenic animal develops and thatremains in the genome of the mature animal, thereby directing theexpression of an encoded gene product in one or more cell types ortissues of the transgenic animal. As used herein, a “homologousrecombinant animal” is a non-human animal, preferably a mammal, morepreferably a mouse, in which an endogenous NOVX gene has been altered byhomologous recombination between the endogenous gene and an exogenousDNA molecule introduced into a cell of the animal, e.g., an embryoniccell of the animal, prior to development of the animal

[0208] A transgenic animal of the invention can be created byintroducing NOVX-encoding nucleic acid into the male pronuclei of afertilized oocyte (e.g. by microinjection, retroviral infection) andallowing the oocyte to develop in a pseudopregnant female foster animal.The human NOVX cDNA sequences, i.e., any one of SEQ ID NO:2n-1, whereinn is an integer between 1 and 44, can be introduced as a transgene intothe genome of a non-human animal. Alternatively, a non-human homologueof the human NOVX gene, such as a mouse NOVX gene, can be isolated basedon hybridization to the human NOVX cDNA (described further supra) andused as a transgene. Intronic sequences and polyadenylation signals canalso be included in the transgene to increase the efficiency ofexpression of the transgene. A tissue-specific regulatory sequence(s)can be operably-linked to the NOVX transgene to direct expression ofNOVX protein to particular cells. Methods for generating transgenicanimals via embryo manipulation and microinjection, particularly animalssuch as mice, have become conventional in the art and are described, forexample, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,44; andHogan, 1986, In: MANIPULATING THE MOUSE EMBRYO, Cold Spring HarborLaboratory Press, Cold Spring Harbor, N.Y. Similar methods are used forproduction of other transgenic animals. A transgenic founder animal canbe identified based upon the presence of the NOVX transgene in itsgenome and/or expression of NOVX mRNA in tissues or cells of theanimals. A transgenic founder animal can then be used to breedadditional animals carrying the transgene. Moreover, transgenic animalscarrying a transgene-encoding NOVX protein can further be bred to othertransgenic animals carrying other transgenes.

[0209] To create a homologous recombinant animal, a vector is preparedwhich contains at least a portion of a NOVX gene into which a deletion,addition or substitution has been introduced to thereby alter, e.g.functionally disrupt, the NOVX gene. The NOVX gene can be a human gene(e.g. the cDNA of any one of SEQ ID NO:2n-1, wherein n is an integerbetween 1 and 44), but more preferably, is a non-human homologue of ahuman NOVX gene. For example, a mouse homologue of human NOVX gene ofSEQ ID NO:2n-1, wherein n is an integer between 1 and 44, can be used toconstruct a homologous recombination vector suitable for altering anendogenous NOVX gene in the mouse genome. In one embodiment, the vectoris designed such that, upon homologous recombination, the endogenousNOVX gene is functionally disrupted (i.e. no longer encodes a functionalprotein also referred to as a “knock out” vector).

[0210] Alternatively, the vector can be designed such that, uponhomologous recombination, the endogenous NOVX gene is mutated orotherwise altered but still encodes functional protein (e.g. theupstream regulatory region can be altered to thereby alter theexpression of the endogenous NOVX protein). In the homologousrecombination vector, the altered portion of the NOVX gene is flanked atits 5′- and 3′-termini by additional nucleic acid of the NOVX gene toallow for homologous recombination to occur between the exogenous NOVXgene carried by the vector and an endogenous NOVX gene in an embryonicstem cell. The additional flanking NOVX nucleic acid is of sufficientlength for successful homologous recombination with the endogenous gene.Typically several kilobases of flanking DNA (both at the 5′- and3′-termini) are included in the vector. See, e.g., Thomas, et al., 1987,Cell 51: 503 for a description of homologous recombination vectors. Thevector is ten introduced into an embryonic stem cell line (e.g., byelectroporation) and cells in which the introduced NOVX gene hashomologously-recombined with the endogenous NOVX gene are selected. See,e.g., Li, et al., 1992, Cell 69: 915.

[0211] The selected cells are then injected into a blastocyst of ananimal (e.g., a mouse) to form aggregation chimeras. See e.g., Bradley,1987, In: TERATOCARCINOMAS AND EMBRYONIC STEM CELLS: A PRACTICALAPPROACH, Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo canthen be implanted into a suitable pseudopregnant female foster animaland the embryo brought to term. Progeny harboring thehomologously-recombined DNA in their germ cells can be used to breedanimals in which all cells of the animal contain thehomologously-recombined DNA by germline transmission of the transgene.Methods for constructing homologous recombination vectors and homologousrecombinant animals are described further in Bradley, 1991, Curr OpinBiotechnol. 2: 823-829; PCT International Publication Nos.: WO 90/11354;WO 91/01140; WO 92/0968; and WO 93/04169.

[0212] In another embodiment, transgenic non-humans animals can beproduced that contain selected systems that allow for regulatedexpression of the transgene. One example of such a system is thecre/loxP recombinase system of bacteriophage P1. For a description ofthe cre/loxP recombinase system. See, e.g., Lakso, et al., 1992, ProcNatl Acad. Sci USA 89: 6232-6236. Another example of a recombinasesystem is the FLP recombinase system of Saccharomyces cerevisiae. See,O'Gorman, et al., 1991, Science 251:1351-1355. If a cre/loxP recombinasesystem is used to regulate expression of the transgene, animalscontaining transgenes encoding both the Cre recombinase and a selectedprotein are required. Such animals can be provided through theconstruction of “double” transgenic animals, e.g., by mating twotransgenic animals, one containing a transgene encoding a selectedprotein and the other containing a transgene encoding a recombinase.

[0213] Clones of the non-human transgenic animals described herein canalso be produced according to the methods described in Wilmut, et al.,1997, Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) fromthe transgenic animal can be isolated and induced to exit the growthcycle and enter G₀ phase. The quiescent cell can then be fused, e.g.,through the use of electrical pulses, to an enucleated oocyte from ananimal of the same species from which the quiescent cell is isolated.The reconstructed oocyte is then cultured such that it develops tomorula or blastocyte and then transferred to pseudopregnant femalefoster animal. The offspring borne of this female foster animal will bea clone of the animal from which the cell (e.g., the somatic cell) isisolated.

[0214] Pharmaceutical Compositions

[0215] The NOVX nucleic acid molecules, NOVX proteins, and anti-NOVXantibodies (also referred to herein as “active compounds”) of theinvention, and derivatives, fragments, analogs and homologs thereof, canbe incorporated into pharmaceutical compositions suitable foradministration. Such compositions typically comprise the nucleic acidmolecule, protein, or antibody and a pharmaceutically acceptablecarrier. As used herein, “pharmaceutically acceptable carrier” isintended to include any and all solvents, dispersion media, coatings,antibacterial and antifungal agents, isotonic and absorption delayingagents, and the like, compatible with pharmaceutical administration.Suitable carriers are described in the most recent edition ofRemington's Pharmaceutical Sciences, a standard reference text in thefield, which is incorporated herein by reference. Preferred examples ofsuch carriers or diluents include, but are not limited to, water,saline, finger's solutions, dextrose solution, and 5% human serumalbumin. Liposomes and non-aqueous vehicles such as fixed oils may alsobe used. The use of such media and agents for pharmaceutically activesubstances is well known in the art. Except insofar as any conventionalmedia or agent is incompatible with the active compound, use thereof inthe compositions is contemplated. Supplementary active compounds canalso be incorporated into the compositions.

[0216] A pharmaceutical composition of the invention is formulated to becompatible with its intended route of administration. Examples of routesof administration include parenteral, e.g. intravenous, intradermal,subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical),transmucosal, and rectal administration. Solutions or suspensions usedfor parenteral, intradermal, or subcutaneous application can include thefollowing components: a sterile diluent such as water for injection,saline solution, fixed oils, polyethylene glycols, glycerine, propyleneglycol or other synthetic solvents; antibacterial agents such as benzylalcohol or methyl parabens; antioxidants such as ascorbic acid or sodiumbisulfite; chelating agents such as ethylenediaminetetraacetic acid(EDTA); buffers such as acetates, citrates or phosphates, and agents forthe adjustment of tonicity such as sodium chloride or dextrose. The pHcan be adjusted with acids or bases, such as hydrochloric acid or sodiumhydroxide. The parenteral preparation can be enclosed in ampoules,disposable syringes or multiple dose vials made of glass or plastic.

[0217] Pharmaceutical compositions suitable for injectable use includesterile aqueous solutions (where water soluble) or dispersions andsterile powders for the extemporaneous preparation of sterile injectablesolutions or dispersion. For intravenous administration, suitablecarriers include physiological saline, bacteriostatic water, CremophorEL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In allcases, the composition must be sterile and should be fluid to the extentthat easy syringeability exists. It must be stable under the conditionsof manufacture and storage and must be preserved against thecontaminating action of microorganisms such as bacteria and fungi. Thecarrier can be a solvent or dispersion medium containing, for example,water, ethanol, polyol (for example, glycerol, propylene glycol, andliquid polyethylene glycol, and the like), and suitable mixturesthereof. The proper fluidity can be maintained, for example, by the useof a coating such as lecithin, by the maintenance of the requiredparticle size in the case of dispersion and by the use of surfactants.Prevention of the action of microorganisms can be achieved by variousantibacterial and antifungal agents, for example, parabens,chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In manycases, it will be preferable to include isotonic agents, for example,sugars, polyalcohols such as manitol, sorbitol, sodium chloride in thecomposition. Prolonged absorption of the injectable compositions can bebrought about by including the composition an agent which delaysabsorption, for example, aluminum monostearate and gelatin.

[0218] Sterile injectable solutions can be prepared by incorporating theactive compound (e.g., a NOVX protein or anti-NOVX antibody) in therequired amount in an appropriate solvent with one or a combination ofingredients enumerated above, as required, followed by filteredsterilization. Generally, dispersions are prepared by incorporating theactive compound into a sterile vehicle that contains a basic dispersionmedium and the required other ingredients from those enumerated above.In the case of sterile powders for the preparation of sterile injectablesolutions, methods of preparation are vacuum drying and freeze-dryingthat yields a powder of the active ingredient plus any additionaldesired ingredient from a previously sterile-filtered solution thereof.

[0219] Oral compositions generally include an inert diluent or an ediblecarrier. They can be enclosed in gelatin capsules or compressed intotablets. For the purpose of oral therapeutic administration, the activecompound can be incorporated with excipients and used in the form oftablets, troches, or capsules. Oral compositions can also be preparedusing a fluid carrier for use as a mouthwash, wherein the compound inthe fluid carrier is applied orally and swished and expectorated orswallowed. Pharmaceutically compatible binding agents, and/or adjuvantmaterials can be included as part of the composition. The tablets,pills, capsules, troches and the like can contain any of the followingingredients, or compounds of a similar nature: a binder such asmicrocrystalline cellulose, gum tragacanth or gelatin; an excipient suchas starch or lactose, a disintegrating agent such as alginic acid,Primogel, or corn starch; a lubricant such as magnesium stearate orSterotes; a glidant such as colloidal silicon dioxide; a sweeteningagent such as sucrose or saccharin; or a flavoring agent such aspeppermint, methyl salicylate, or orange flavoring.

[0220] For administration by inhalation, the compounds are delivered inthe form of an aerosol spray from pressured container or dispenser whichcontains a suitable propellant, e.g., a gas such as carbon dioxide, or anebulizer.

[0221] Systemic administration can also be by transmucosal ortransdermal means. For transmucosal or transdermal administration,penetrants appropriate to the barrier to be permeated are used in theformulation. Such penetrants are generally known in the art, andinclude, for example, for transmucosal administration, detergents, bilesalts, and fusidic acid derivatives. Transmucosal administration can beaccomplished through the use of nasal sprays or suppositories. Fortransdermal administration, the active compounds are formulated intoointments, salves, gels, or creams as generally known in the art.

[0222] The compounds can also be prepared in the form of suppositories(e.g. with conventional suppository bases such as cocoa butter and otherglycerides) or retention enemas for rectal delivery.

[0223] In one embodiment, the active compounds are prepared withcarriers that will protect the compound against rapid elimination fromthe body, such as a controlled release formulation, including implantsand microencapsulated delivery systems. Biodegradable, biocompatiblepolymers can be used, such as ethylene vinyl acetate, polyanhydrides,polyglycolic acid, collagen, polyorthoesters, and polylactic acid.Methods for preparation of such formulations will be apparent to thoseskilled in the art. The materials can also be obtained commercially fromAlza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions(including, liposomes targeted to infected cells with monoclonalantibodies to viral antigens) can also be used as pharmaceuticallyacceptable carriers. These can be prepared according to methods known tothose skilled in the art, for example, as described in U.S. Pat. No.4,522,811.

[0224] It is especially advantageous to formulate oral or parenteralcompositions in dosage unit form for ease of administration anduniformity of dosage. Dosage unit form as used herein refers tophysically discrete units suited as unitary dosages for the subject tobe treated; each unit containing a predetermined quantity of activecompound calculated to produce the desired therapeutic effect inassociation with the required pharmaceutical carrier. The specificationfor the dosage unit forms of the invention are dictated by and directlydependent on the unique characteristics of the active compound and theparticular therapeutic effect to be achieved, and the limitationsinherent in the art of compounding such an active compound for thetreatment of individuals.

[0225] The nucleic acid molecules of the invention can be inserted intovectors and used as gene therapy vectors. Gene therapy vectors can bedelivered to a subject by, for example, intravenous injection, localadministration (see, e.g. U.S. Pat. No. 5,328,470) or by stereotacticinjection (see, e.g. Chen, et al., 1994, Proc. Natl. Acad. Sci. USA 91:3054-3057). The pharmaceutical preparation of the gene therapy vectorcan include the gene therapy vector in an acceptable diluent, or cancomprise a slow release matrix in which the gene delivery vehicle isimbedded. Alternatively, where the complete gene delivery vector can beproduced intact from recombinant cells, e.g., retroviral vectors, thepharmaceutical preparation can include one or more cells that producethe gene delivery system.

[0226] The pharmaceutical compositions can be included in a container,pack, or dispenser together with instructions for administration.

[0227] Screening and Detection Methods

[0228] The isolated nucleic acid molecules of the invention can be usedto express NOVX protein (e.g. via a recombinant expression vector in ahost cell in gene therapy applications), to detect NOVX mRNA (e.g. in abiological sample) or a genetic lesion in a NOVX gene, and to modulateNOVX activity, as described further, below. In addition, the NOVXproteins can be used to screen drugs or compounds that modulate the NOVXprotein activity or expression as well as to treat disorderscharacterized by insufficient or excessive production of NOVX protein orproduction of NOVX protein forms that have decreased or aberrantactivity compared to NOVX wild-type protein (e.g.; diabetes (regulatesinsulin release); obesity (binds and transport lipids); metabolicdisturbances associated with obesity, the metabolic syndrome X as wellas anorexia and wasting disorders associated with chronic diseases andvarious cancers, and infectious disease(possesses anti-microbialactivity) and the various dyslipidemias. In addition, the anti-NOVXantibodies of the invention can be used to detect and isolate NOVXproteins and modulate NOVX activity. In yet a further aspect, theinvention can be used in methods to influence appetite, absorption ofnutrients and the disposition of metabolic substrates in both a positiveand negative fashion.

[0229] The invention further pertains to novel agents identified by thescreening assays described herein and uses thereof for treatments asdescribed, supra.

[0230] Screening Assays

[0231] The invention provides a method (also referred to herein as a“screening assay”) for identifying modulators, i.e., candidate or testcompounds or agents (e.g. peptides, peptidomimetics, small molecules orother drugs) that bind to NOVX proteins or have a stimulatory orinhibitory, effect on, e.g. NOVX protein expression or NOVX proteinactivity. The invention also includes compounds identified in thescreening assays described herein.

[0232] In one embodiment, the invention provides assays for screeningcandidate or test compounds which bind to or modulate the activity ofthe membrane-bound form of a NOVX protein or polypeptide orbiologically-active portion thereof. The test compounds of the inventioncan be obtained using any of the numerous approaches in combinatoriallibrary methods known in the art, including: biological libraries;spatially addressable parallel solid phase or solution phase libraries;synthetic library methods requiring deconvolution; the “one-beadone-compound” library method; and synthetic library methods usingaffinity chromatography selection. The biological library approach islimited to peptide libraries, while the other four approaches areapplicable to peptide, non-peptide oligomer or small molecule librariesof compounds. See, e.g. Lam, 1997, Anticancer Drug Design 12: 145.

[0233] A “small molecule” as used herein, is meant to refer to acomposition that has a molecular eight of less than about 5 kD and mostpreferably less than about 4 kD. Small molecules can be, e.g., nucleicacids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids orother organic or inorganic molecules. Libraries of chemical and/orbiological mixtures, such as fungal, bacterial, or algal extracts, areknown in the art and can be screened with any of the assays of theinvention.

[0234] Examples of methods for the synthesis of molecular libraries canbe found in the art, for example in DeWitt, et al., 1993, Proc. Natl.Acad Sci. USA, 90: 6909; Erb, et al., 1994, Proc. Natl. Acad Sci U.S.A.91: 11422; Zuckermann, et al., 1994, J. Med Chem 37: 2678; Cho, et al.,1993, Science 261: 1303; Carrell, et al., 1994, Angew. Chem Int Ed. Engl33: 2059; Carell, et al., 1994 Angew. Chem. Int. Ed. Engl. 33: 2061; andGallop, et al., 1994, J Med Chem 37: 1233.

[0235] Libraries of compounds may be presented in solution (e.g.,Houghten 1992, Biotechniques 13: 412-421), or on beads (Lam, 1991,Nature 354: 82-84), on chips (Fodor, 1993, Nature 364: 555-556),bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat.No. 5,233,409), plasmids (Cull, et al., 1992, Proc. Natl. Acad. Sci (USA89: 1865-1869) or on phage (Scott and Smith, 1990, Science 249: 386-390;Devlin, 1990, Science 249: 404-406; Cwirla, et al., 1990, Proc Natl AcadSci. U.S.A. 87: 6378-6382; Felici, 1991, J Mol Biol 222: 301-310;Ladner, U.S. Pat. No. 5,233,409.).

[0236] In one embodiment, an assay is a cell-based assay in which a cellwhich expresses a membrane-bound form of NOVX protein, or abiologically-active portion thereof, on the cell surface is contactedwith a test compound and the ability of the test compound to bind to aNOVX protein determined. The cell, for example, can of mammalian originor a yeast cell. Determining the ability of the test compound to bind tothe NOVX protein can be accomplished, for example, by coupling the testcompound with a radioisotope or enzymatic label such that binding of thetest compound to the NOVX protein or biologically-active portion thereofcan be determined by detecting the labeled compound in a complex. Forexample, test compounds can be labeled with ¹²⁵I, ³⁵S, ¹⁴C, or ³H,either directly or indirectly, and the radioisotope detected by directcounting of radioemission or by scintillation counting. Alternatively,test compounds can be enzymatically-labeled with, for example,horseradish peroxidase, alkaline phosphatase, or luciferase, and theenzymatic label detected by determination of conversion of anappropriate substrate to product. In one embodiment, the assay comprisescontacting a cell which expresses a membrane-bound form of NOVX protein,or a biologically-active portion thereof, on the cell surface with aknown compound which binds NOVX to form an assay mixture, contacting,the assay mixture with a test compound, and determining the ability ofthe test compound to interact with a NOVX protein, herein determiningthe ability of the test compound to interact with a NOVX proteincomprises determining the ability of the test compound to preferentiallybind to NOVX protein or a biologically-active portion thereof ascompared to the known compound.

[0237] In another embodiment, an assay is a cell-based assay comprisingcontacting, a cell expressing a membrane-bound form of NOVX protein, ora biologically-active portion thereof, on the cell surface with a testcompound and determining the ability of the test compound to modulate(e.g., stimulate or inhibit) the activity of the NOVX protein orbiologically-active portion thereof. Determining the ability of the testcompound to modulate the activity of NOVX or a biologically-activeportion thereof can be accomplished, for example, by determining theability of the NOVX protein to bind to or interact with a NOVX targetmolecule. As used herein, a “target molecule” is a molecule with which aNOVX protein binds or interacts in nature, for example, a molecule onthe surface of a cell which expresses a NOVX interacting protein, amolecule on the surface of a second cell, a molecule in theextracellular milieu, a molecule associated with the internal surface ofa cell membrane or a cytoplasmic molecule. A NOVX target molecule can bea non-NOVX molecule or a NOVX protein or polypeptide of the invention.In one embodiment, a NOVX target molecule is a component of a signaltransduction pathway that facilitates transduction of an extracellularsignal (e.g. a signal generated by binding of a compound to amembrane-bound NOVX molecule) through the cell membrane and into thecell. The target, for example, can be a second intercellular proteinthat has catalytic activity or a protein that facilitates theassociation of downstream signaling molecules with NOVX.

[0238] Determining the ability or the NOVX protein to bind to orinteract with a NOVX target molecule can be accomplished by one of themethods described above for determining direct binding. In oneembodiment, determining the ability of the NOVX protein to bind to orinteract with a NOVX target molecule can be accomplished by determiningthe activity of the target molecule. For example, the activity of thetarget molecule can be determined by detecting induction of a cellularsecond messenger of the target (i.e. intracellular Ca²⁺, diacylglycerol,IP₃, etc.), detecting catalytic/enzymatic activity of the target anappropriate substrate, detecting the induction of a reporter gene(comprising a NOVX-responsive regulatory element operatively linked to anucleic acid encoding a detectable marker, e.g. luciferase), ordetecting a cellular response, for example, cell survival, cellulardifferentiation, or cell proliferation.

[0239] In yet another embodiment, an assay of the invention is acell-free assay comprising contacting a NOVX protein orbiologically-active portion thereof with a test compound and determiningthe ability of the test compound to bind to the NOVX protein orbiologically-active portion thereof. Binding of the test compound to theNOVX protein can be determined either directly or indirectly asdescribed above. In one such embodiment, the assay comprises contactingthe NOVX protein or biologically-active portion thereof with a knowncompound which binds NOVX to form an assay mixture, contacting the assaymixture with a test compound, and determining the ability of the testcompound to interact with a NOVX protein, wherein determining theability of the test compound to interact with a NOVX protein comprisesdetermining the ability of the test compound to preferentially bind toNOVX or biologically-active portion thereof as compared to the knowncompound.

[0240] In still another embodiment, an assay is a cell-free assaycomprising contacting NOVX protein or biologically-active portionthereof with a test compound and determining the ability of the testcompound to modulate (e.g. stimulate or inhibit) the activity of theNOVX protein or biologically-active portion thereof. Determining theability of the test compound to modulate the activity of NOVX can beaccomplished, for example, by determining the ability of the NOVXprotein to bind to a NOVX target molecule by one of the methodsdescribed above for determining direct binding. In an alternativeembodiment, determining the ability of the test compound to modulate theactivity of NOVX protein can be accomplished by determining the abilityof the NOVX protein further modulate a NOVX target molecule. Forexample, the catalytic/enzymatic activity of the target molecule on anappropriate substrate can be determined as described, supra.

[0241] In yet another embodiment, the cell-free assay comprisescontacting the NOVX protein or biologically-active portion thereofwithin a known compound which binds NOVX protein to form an assaymixture, contacting the assay mixture with a test compound, anddetermining the ability of the test compound to interact with a NOVXprotein, wherein determining the ability of the test compound tointeract with a NOVX protein comprises determining the ability of theNOVX protein to preferentially bind to or modulate the activity of aNOVX target molecule.

[0242] The cell-free assays of the invention are amenable to use of boththe soluble form or the membrane-bound form of NOVX protein. In the caseof cell-free assays comprising the membrane-bound form of NOVX protein,it may be desirable to utilize a solubilizing agent such that themembrane-bound form of NOVX protein is maintained in solution. Examplesof such solubilizing agents include non-ionic detergents such asn-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside,octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100,Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)_(n),N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate,3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate(CHAPSO).

[0243] In more than one embodiment of the above assay methods of theinvention, it may be desirable to immobilize either NOVX protein or itstarget molecule to facilitate separation of complexed from uncomplexedforms of one or both of the proteins, as well as to accommodateautomation of the assay. Binding of a test compound to NOVX protein, orinteraction of NOVX protein with a target molecule in the presence andabsence of a candidate compound, can be accomplished in any vesselsuitable for containing the reactants. Examples of such vessels includemicrotiter plates, test tubes, and micro-centrifuge tubes. In oneembodiment, a fusion protein can be provided that adds a domain thatallows one or both of the proteins to be bound to a matrix. For example,GST-NOVX fusion proteins or GST-target fusion proteins can be adsorbedonto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) orglutathione derivatized microtiter plates, that are then combined withthe test compound or the test compound and either the non-adsorbedtarget protein or NOVX protein, and the mixture is incubated underconditions conducive to complex formation (e.g., at physiologicalconditions for salt and pH). Following incubation, the beads ormicrotiter plate wells are washed to remove any unbound components, thematrix immobilized in the case of beads, complex determined eitherdirectly or indirectly, for example, as described, supra. Alternatively,the complexes can be dissociated from the matrix, and the level of NOVXprotein binding or activity determined using standard techniques.

[0244] Other techniques for immobilizing proteins on matrices can alsobe used in the screening assays of the invention. For example, eitherthe NOVX protein or its target molecule can be immobilized utilizingconjugation of biotin and streptavidin. Biotinylated NOVX protein ortarget molecules can be prepared from biotin-NHS (N-hydroxy-succinimide)using,techniques well-known within the art (e.g. biotinylation kit,Pierce Chemicals, Rockford, Ill.), and immobilized in the wells ofstreptavidin-coated 96 well plates (Pierce Chemical). Alternatively,antibodies reactive with NOVX protein or target molecules, but which donot interfere with binding of the NOVX protein to its target molecule,can be derivatized to the wells of the plate, and unbound target or NOVXprotein trapped in the wells by antibody conjugation. Methods fordetecting such complexes, in addition to those described above for theGST-immobilized complexes, include immunodetection of complexes usingantibodies reactive with the NOVX protein or target molecule, as well asenzyme-linked assays that rely on detecting an enzymatic activityassociated with the NOVX protein or target molecule.

[0245] In another embodiment, modulators of NOVX protein expression areidentified in a method wherein a cell is contacted with a candidatecompound and the expression of NOVX mRNA or protein in the cell isdetermined. The level of expression of NOVX mRNA or protein in thepresence of the candidate compound is compared to the level ofexpression of NOVX mRNA or protein in the absence of the candidatecompound. The candidate compound can then be identified as a modulatorof NOVX mRNA or protein expression based upon this comparison. Forexample, when expression of NOVX mRNA or protein is greater (i.e.,statistically significantly greater) in the presence of the candidatecompound than in its absence, the candidate compound is identified as astimulator of NOVX mRNA or protein expression. Alternatively, whenexpression of NOVX mRNA or protein is less (statistically significantlyless) in the presence of the candidate compound than in its absence, thecandidate compound is identified as an inhibitor of NOVX mRNA or proteinexpression. The level of NOVX mRNA or protein expression in the cellscan be determined by methods described herein for detecting NOVX mRNA orprotein.

[0246] In yet another aspect of the invention, the NOVX proteins can beused as “bait proteins” in a two-hybrid assay or three hybrid assay(see, e.g., U.S. Pat. No 5,283,317; Zervos, et al., 1993, Cell 72:223-232; Madura, et al., 1993, J Biol Chem 268: 12046-12054; Bartel, etal., 1993, Biotechniques 14: 920-924; Iwabuchi, et al., 1993, Oncogene8: 1693-1696; and Brent WO94/10300), to identify other proteins thatbind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) andmodulate NOVX activity. Such NOVX-binding proteins are also involved inthe propagation of signals by the NOVX proteins as, for example,upstream or downstream elements of the NOVX pathway.

[0247] The two-hybrid system is based on the modular nature of mosttranscription factors, which consist of separable DNA-binding andactivation domains. Briefly, the assay utilizes two different DNAconstructs. In one construct, the gene that codes for NOVX is fused to agene encoding the DNA binding domain of a known transcription factor(e.g., GAL-4). In the other construct, a DNA sequence, from a library ofDNA sequences, that encodes an unidentified protein (“prey” or “sample”)is fused to a gene that codes for the activation domain of the knowntranscription factor. If the “bait” and the “prey” proteins are able tointeract, in vivo, forming a NOVX-dependent complex, the DNA-binding andactivation domains of the transcription factor are brought into closeproximity. This proximity allows transcription of a reporter gene (e.g.,LacZ) that is operably linked to a transcriptional regulatory siteresponsive to the transcription factor. Expression of the reporter genecan be detected and cell colonies containing the functionaltranscription factor can be isolated and used to obtain the cloned genethat encodes the protein which interacts with NOVX.

[0248] The invention further pertains to novel agents identified by theaforementioned screening assays and uses thereof for treatments asdescribed herein.

[0249] Detection Assays

[0250] Portions or fragments of the cDNA sequences identified herein(and the corresponding complete gene sequences) can be used in numerousways as polynucleotide reagents. By way of example, and not oflimitation, these sequences can be used to: (i) map their respectivegenes on a chromosome; and, thus, locate gene regions associated withgenetic disease; (ii) identify an individual from a minute biologicalsample (tissue typing); and (iii) aid in forensic identification of abiological sample. Some of these applications are described in thesubsections, below.

[0251] Chromosome Mapping

[0252] Once the sequence (or a portion of the sequence) of a gene hasbeen isolated, this sequence can be used to map the location of the geneon a chromosome. This process is called chromosome mapping. Accordingly,portions or fragments of the NOVX sequences of SEQ ID NO:2n-1, wherein nis an integer between 1 and 44, or fragments or derivatives thereof, canbe used to map the location of the NOVX genes, respectively, on achromosome. The mapping of the NOVX sequences to chromosomes is animportant first step in correlating these sequences with genesassociated with disease.

[0253] Briefly, NOVX genes can be mapped to chromosomes by preparing PCRprimers (preferably 15-25 bp in length) from the NOVX sequences.Computer analysis of the NOVX, sequences can be used to rapidly selectprimers that do not span more than one exon in the genomic DNA, thuscomplicating the amplification process. These primers can then be usedfor PCR screening of somatic cell hybrids containing individual humanchromosomes. Only those hybrids containing the human gene correspondingto the NOVX sequences will yield an amplified fragment.

[0254] Somatic cell hybrids are prepared by fusing somatic cells fromdifferent mammals (e.g., human and mouse cells). As hybrids of human andmouse cells grow and divide, they gradually lose human chromosomes inrandom order, but retain the mouse chromosomes. By using media in whichmouse cells cannot grow, because they lack a particular enzyme, but inwhich human cells can, the one human chromosome that contains the geneencoding the needed enzyme will be retained. By using various media,panels of hybrid cell lines can be established. Each cell line in apanel contains either a single human chromosome or a small number ofhuman chromosomes, and a full set of mouse chromosomes, allowing easymapping of individual genes to specific human chromosomes. See, e.g.,D'Eustachio, et al., 1983, Science 220: 919-924. Somatic cell hybridscontaining only fragments of human chromosomes can also be produced byusing human chromosomes with translocations and deletions.

[0255] PCR mapping of somatic cell hybrids is a rapid procedure forassigning a particular sequence to a particular chromosome. Three ormore sequences can be assigned per day using a single thermal cycler.Using the NOVX sequences to design oligonucleotide primers,sub-localization can be achieved with panels of fragments from specificchromosomes.

[0256] Fluorescence in situ hybridization (FISH) of a DNA sequence to ametaphase chromosomal spread can further be used to provide a precisechromosomal location in one step. Chromosome spreads can be made usingcells whose division has been blocked in metaphase by a chemical likecolcemid that disrupts the mitotic spindle. The chromosomes can betreated briefly with trypsin, and then stained with Giemsa. A pattern oflight and dark bands develops on each chromosome, so that thechromosomes can be identified individually. The FISH technique can beused with a DNA sequence as short as 500 or 600 bases. However, cloneslarger than 1,000 bases have a higher likelihood of binding to a uniquechromosomal location with sufficient signal intensity for simpledetection. Preferably 1,000 bases, and more preferably 2,000 bases, willsuffice to get good results at a reasonable amount of time. For a reviewof this technique, see, Verma, et al., HUMAN CHROMOSOMES: A MANUAL OFBASIC TECHNIQUES (Pergamon Press, New York 1988).

[0257] Reagents for chromosome mapping can be used individually to marka single chromosome or a single site on that chromosome, or panels ofreagents can be used for marking multiple sites and/or multiplechromosomes. Reagents corresponding to noncoding, regions of the genesactually are preferred for mapping purposes. Coding sequences are morelikely to be conserved within gene families, thus increasing the chanceof cross hybridizations during chromosomal mapping.

[0258] Once a sequence has been mapped to a precise chromosomallocation, the physical position of the sequence on the chromosome can becorrelated with genetic map data. Such data are found e.g., in McKusick,MENDELIAN INHERITANCE IN MAN, available on-line through Johns HopkinsUniversity Welch Medical Library). The relationship between genes anddisease, mapped to the same chromosomal region, can then be identifiedthrough linkage analysis (co-inheritance of physically adjacent genes),described in, e.g., Egeland, et al., 1987, Nature, 325: 783-787.

[0259] Moreover, differences in the DNA sequences between individualsaffected and unaffected with a disease associated with the NOVX gene,can be determined. If a mutation is observed in some or all of theaffected individuals but not in any unaffected individuals, then themutation is likely to be the causative agent of the particular disease.Comparison of affected and unaffected individuals generally involvesfirst looking for structural alterations in the chromosomes, such asdeletions or translocations that are visible from chromosome spreads ordetectable using PCR based on that DNA sequence. Ultimately, completesequencing of genes from several individuals can be performed to confirmthe presence of a mutation and to distinguish mutations frompolymorphisms.

[0260] Tissue Typing

[0261] The NOVX sequences of the invention can also be used to identifyindividuals from minute biological samples. In this technique, anindividual's genomic DNA is digested with one or more restrictionenzymes, and probed on a Southern blot to yield unique bands foridentification. The sequences of the invention are useful as additionalDNA markers for RFLP (“restriction fragment length polymorphisms,”described in U.S. Pat. No. 5,272,057).

[0262] Furthermore, the sequences of the invention can be used toprovide an alternative technique that determines the actual base-by-baseDNA sequence of selected portions of an individual's genome. Thus, theNOVX sequences described herein can be used to prepare two PCR primersfrom the 5′- and 3′-termini of the sequences. These primers can then beused to amplify an individual's DNA and subsequently sequence it.

[0263] Panels of corresponding DNA sequences from individuals, preparedin this manner, can provide unique individual identifications, as eachindividual will have a unique set of such DNA sequences due to allelicdifferences. The sequences of the invention can be used to obtain suchidentification sequences from individuals and from tissue. The NOVXsequences of the invention uniquely represent portions of the humangenome. Allelic variation occurs to some degree in the coding regions ofthese sequences, and to a greater degree in the noncoding regions. It isestimated that allelic variation between individual humans occurs with afrequency of about once per each 500 bases. Much of the allelicvariation is due to single nucleotide polymorphisms (SNPs), whichinclude restriction fragment length polymorphisms (RFLPs).

[0264] Each of the sequences described herein can, to some degree, beused as a standard against which DNA from an individual can be comparedfor identification purposes. Because greater numbers of polymorphismsoccur in the noncoding regions, fewer sequences are necessary todifferentiate individuals. The noncoding sequences can comfortablyprovide positive individual identification with a panel of perhaps 10 to1,000 primers that each yield a noncoding amplified sequence of 100bases. If coding sequences, such as those of SEQ ID NO:2n-1, wherein nis an integer between 1 and 44, are used, a more appropriate number ofprimers for positive individual identification would be 500-2,000.

[0265] Predictive Medicine

[0266] The invention also pertains to the field of predictive medicinein which diagnostic assays, prognostic assays, pharmacogenomics, andmonitoring clinical trials are used for prognostic (predictive) purposesto thereby treat an individual prophylactically. Accordingly, one aspectof the invention relates to diagnostic assays for determining NOVXprotein and/or nucleic acid expression as well as NOVX activity, in thecontext of a biological sample (e.g., blood, serum, cells, tissue) tothereby determine whether an individual is afflicted with a disease ordisorder, or is at risk of developing a disorder, associated withaberrant NOVX expression or activity. The disorders include metabolicdisorders, diabetes, obesity, infectious disease, anorexia,cancer-associated cachexia, cancer, neurodegenerative disorders,Alzheimer's Disease, Parkinson's Disorder, immune disorders, andhematopoietic disorders, and the various dyslipidemias, metabolicdisturbances associated with obesity, the metabolic syndrome X andwasting disorders associated with chronic diseases and various cancers.The invention also provides for prognostic (or predictive) assays fordetermining whether an individual is at risk of developing a disorderassociated with NOVX protein, nucleic acid expression or activity. Forexample, mutations in a NOVX scene can be assayed in a biologicalsample. Such assays can be used for prognostic or predictive purpose tothereby prophylactically treat an individual prior to the onset of adisorder characterized by or associated with NOVX protein, nucleic acidexpression, or biological activity.

[0267] Another aspect of the invention provides methods for determiningNOVX protein, nucleic acid expression or activity in an individual tothereby select appropriate therapeutic or prophylactic agents for thatindividual (referred to herein as “pharmacogenomics”). Pharmacogenomicsallows for the selection of agents (e.g., drugs) for therapeutic orprophylactic treatment of an individual based on the genotype of theindividual (e.g., the genotype of the individual examined to determinethe ability of the individual to respond to a particular agent.)

[0268] Yet another aspect of the invention pertains to monitoring theinfluence of agents (e.g. drugs, compounds) oil the expression oractivity of NOVX in clinical trials.

[0269] These and other agents are described in further detail in thefollowing sections.

[0270] Diagnostic Assays

[0271] An exemplary method for detecting the presence or absence of NOVXin a biological sample involves obtaining a biological sample from atest subject and contacting the biological sample with a compound or anagent capable of detecting NOVX protein or nucleic acid (e.g., mRNA,genomic DNA) that encodes NOVX protein such that the presence of NOVX isdetected in the biological sample An agent for detecting NOVX mRNA orgenomic DNA is a labeled nucleic acid probe capable of hybridizing toNOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, afull-length NOVX nucleic acid, such as the nucleic acid of SEQ IDNO:2n-1, wherein n is an integer between 1 and 44, or a portion thereof,such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500nucleotides in length and sufficient to specifically hybridize understringent conditions to NOVX mRNA or genomic DNA. Other suitable probesfor use in the diagnostic assays of the invention are described herein.

[0272] An agent for detecting, NOVX protein is an antibody capable ofbinding to NOVX protein, preferably an antibody with a detectable label.Antibodies can be polyclonal, or more preferably monoclonal. An intactantibody, or a fragment thereof (e.g., Fab or F(ab′)₂) can be used. Theterm “labeled”, with regard to the probe or antibody, is intended toencompass direct labeling of the probe or antibody by coupling (i.e.physically linking) a detectable substance to the probe or antibody, aswell as indirect labeling of the probe or antibody by reactivity withanother reagent that is directly labeled. Examples of indirect labelinginclude detection of a primary antibody using a fluorescently-labeledsecondary antibody and end-labeling of a DNA probe with biotin such thatit can be detected with fluorescently-labeled streptavidin. The tern“biological sample” is intended to include tissues, cells and biologicalfluids isolated from a subject, as well as tissues, cells and fluidspresent within a subject. That is, the detection method of the inventioncan be used to detect NOVX mRNA, protein, or genomic DNA in a biologicalsample in in vitro as well as in vivo. For example, in vitro techniquesfor detection of NOVX mRNA include Northern hybridizations and in situhybridizations. In vitro techniques for detection of NOVX proteininclude enzyme linked immunosorbent assays (ELISAs). Western blots,immunoprecipitations, and immunofluorescence. In vitro techniques fordetection of NOVX genomic DNA include Southern hybridizations.Furthermore, in vivo techniques for detection of NOVX protein includeintroducing into a subject a labeled anti-NOVX antibody. For example,the antibody can be labeled with a radioactive marker whose presence andlocation in a subject can be detected by standard imaging techniques.

[0273] In one embodiment, the biological sample contains proteinmolecules from the test subject. Alternatively, the biological samplecan contain mRNA molecules from the test subject or genomic DNAmolecules from the test subject. A preferred biological sample is aperipheral blood leukocyte sample isolated by conventional means from asubject.

[0274] In another embodiment, the methods further involve obtaining acontrol biological sample from a control subject, contacting the controlsample with a compound or agent capable of detecting NOVX protein, mRNA,or genomic DNA, such that the presence of NOVX protein, mRNA or genomicDNA is detected in the biological sample, and comparing the presence ofNOVX protein, mRNA or genomic DNA in the control sample with thepresence of NOVX protein, mRNA or genomic DNA in the test sample.

[0275] The invention also encompasses kits for detecting the presence ofNOVX in a biological sample. For example, the kit can comprise: alabeled compound or agent capable of detecting NOVX protein or mRNA in abiological sample; means for determining the amount of NOVX in thesample; and means for comparing the amount of NOVX in the sample with astandard. The compound or agent can be packaged in a suitable container.The kit can further comprise instructions for using the kit to detectNOVX protein or nucleic acid.

[0276] Prognostic Assays

[0277] The diagnostic methods described herein can furthermore beutilized to identify subjects having or at risk of developing a diseaseor disorder associated with aberrant NOVX expression or activity. Forexample, the assays described herein, such as the preceding diagnosticassays or the following assays, can be utilized to identify a subjecthaving or at risk of developing a disorder associated with NOVX protein,nucleic acid expression or activity. Alternatively, the prognosticassays can be utilized to identify a subject having or at risk fordeveloping a disease or disorder. Thus, the invention provides a methodfor identifying a disease or disorder associated with aberrant NOVXexpression or activity in which a test sample is obtained from a subjectand NOVX protein or nucleic acid (e.g. mRNA, genomic DNA) is detected,wherein the presence of NOVX protein or nucleic acid is diagnostic for asubject having or at risk of developing a disease or disorder associatedwith aberrant NOVX expression or activity. As used herein, a “testsample” refers to a biological sample obtained from a subject ofinterest. For example, a test sample can be a biological fluid (e.g.,serum), cell sample, or tissue.

[0278] Furthermore, the prognostic assays described herein can be usedto determine whether a subject can be administered an agent (e.g. anagonist, antagonist, peptidomimetic, protein, peptide, nucleic acid,small molecule, or other drug candidate) to treat a disease or disorderassociated with aberrant NOVX expression or activity. For example, suchmethods can be used to determine whether a subject can be effectivelytreated with an agent for a disorder. Thus, the invention providesmethods for determining whether a subject can be effectively treatedwith an agent for a disorder associated with aberrant NOVX expression oractivity in which a test sample is obtained and NOVX protein or nucleicacid is detected (e.g., wherein the presence of NOVX protein or nucleicacid is diagnostic for a subject that can be administered the agent totreat a disorder associated with aberrant NOVX expression or activity).

[0279] The methods of the invention can also be used to detect geneticlesions in a NOVX gene, thereby determining if a subject with thelesioned gene is at risk for a disorder characterized by aberrant cellproliferation and/or differentiation. In various embodiments, themethods include detecting, in a sample of cells from the subject, thepresence or absence of a genetic lesion characterized by at least one ofan alteration affecting the integrity of a gene encoding a NOVX-protein,or the misexpression of the NOVX gene. For example, such genetic lesionscan be detected by ascertaining the existence of at least one of: (i) adeletion of one or more nucleotides from a NOVX gene; (ii) an additionof one or more nucleotides to a NOVX gene; (iii) a substitution of oneor more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement ofa NOVX gene; (v) an alteration in the level of a messenger RNAtranscript of a NOVX gene, (vi) aberrant modification of a NOVX gene,such as of the methylation pattern of the genomic DNA, (vii) thepresence of a non-wild-type splicing pattern of a messenger RNAtranscript of a NOVX gene, (viii) a non-wild-type level of a NOVXprotein, (ix) allelic loss of a NOVX gene, and (x) inappropriatepost-translational modification of a NOVX protein. As described herein,there are a large number of assay techniques known in the art which canbe used for detecting lesions in a NOVX gene. A preferred biologicalsample is a peripheral blood leukocyte sample isolated by conventionalmeans from a subject. However, any biological sample containing,nucleated cells may be used, including, for example, buccal mucosalcells.

[0280] In certain embodiments, detection of the lesion involves the useof a probe/primer in a polymerase chain reaction (PCR) (see, e.g. U.S.Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or,alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran,et al., 1988, Science 241: 1077-1080; and Nakazawa, et al., 1994, ProcNatl Acad Sci USA 91: 360-364), the latter of which can be particularlyuseful for detecting point mutations in the NOVX-gene (see, Abravaya, etal., 1995, Nucl Acids Res. 23: 675-682). This method can include thesteps of collecting a sample of cells from a patient, isolating nucleicacid (e.g. genomic, mRNA or both) from the cells of the sample,contacting the nucleic acid sample with one or more primers thatspecifically hybridize to a NOVX gene under conditions such thathybridization and amplification of the NOVX gene (if present) occurs,and detecting the presence or absence of an amplification product, ordetecting the size of the amplification product and comparing the lengthto a control sample. It is anticipated that PCR and/or LCR may bedesirable to use as a preliminary amplification step in conjunction withany of the techniques used for detecting mutations described herein.

[0281] Alternative amplification methods include: self sustainedsequence replication (see, Guatelli, et al., 1990, Proc. Natl Acad Sci.USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, etal., 1989, Proc. Natl. Acad Sci. USA 86: 1173-1177); Qβ Replicase (see,Lizardi, et al. 1988, BioTechnology 6: 1197), or any other nucleic acidamplification method, followed by the detection of the amplifiedmolecules using techniques well known to those of skill in the art.These detection schemes are especially useful for the detection ofnucleic acid molecules if such molecules are present in very lownumbers.

[0282] In an alternative embodiment, mutations in a NOVX gene from asample cell can be identified by alterations in restriction enzymecleavage patterns. For example, sample and control DNA is isolated,amplified (optionally), digested with one or more restrictionendonucleases, and fragment length sizes are determined by gelelectrophoresis and compared. Differences in fragment length sizesbetween sample and control DNA indicates mutations in the sample DNA.Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Pat.No. 5,493,531) can be used to score for the presence of specificmutations by development or loss of a ribozyme cleavage site.

[0283] In other embodiments, genetic mutations in NOVX can be identifiedby hybridizing a sample and control nucleic acids, e.g. DNA or RNA, tohigh-density arrays containing hundreds or thousands of oligonucleotidesprobes. See, e.g., Cronin, et al., 1996, Human Mutation 7: 244-255;Kozal, et al., 1996, Nat Med 2: 753-759. For example, genetic mutationsin NOVX can be identified in two dimensional arrays containinglight-generated DNA probes as described in Cronin, et al., supra.Briefly, a first hybridization array of probes can be used to scanthrough long stretches of DNA in a sample and control to identify basechanges between the sequences by making linear arrays of sequentialoverlapping probes. This step allows the identification of pointmutations. This is followed by a second hybridization array that allowsthe characterization of specific mutations by using smaller, specializedprobe arrays complementary to all variants or mutations detected. Eachmutation array is composed of parallel probe sets, one complementary tothe wild-type gene and the other complementary to the mutant gene.

[0284] In yet another embodiment, any of a variety of sequencingreactions known in the art can be used to directly sequence the NOVXgene and detect mutations by comparing the sequence of the sample NOVXwith the corresponding wild-type (control) sequence. Examples ofsequencing reactions include those based on techniques developed byMaxim and Gilbert, 1977, Proc Natl. Acad. Sci USA 74: 560 or Sanger,1977, Proc. Natl Acad Sci. USA 74: 5463. It is also contemplated thatany of a variety of automated sequencing procedures can be utilized whenperforming the diagnostic assays (see, e.g. Naeve, et al., 1995,Biotechniques 19: 448), including sequencing by mass spectrometry (see,e.g. PCT International Publication No. WO 94/16101; Cohen, et al., 1996,Adv. Chromatography 36: 127-162; and Griffin, et al., 1993, Appl BiochemBiotechnol 38: 147-159).

[0285] Other methods for detecting mutations in the NOVX gene includemethods in which protection from cleavage agents is used to detectmismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers,et al., 1985, Science 230: 1242. In general, the art technique of“mismatch cleavage” starts by providing heteroduplexes of formed byhybridizing (labeled) RNA or DNA containing the wild-type NOVX sequencewith potentially mutant RNA or DNA obtained from a tissue sample. Thedouble-stranded duplexes are treated with an agent that cleavessingle-stranded regions of the duplex such as which will exist due tobasepair mismatches between the control and sample strands. Forinstance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybridstreated with S₁ nuclease to enzymatically digesting the mismatchedregions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can betreated with hydroxylamine or osmium tetroxide and with piperidine inorder to digest mismatched regions. After digestion of the mismatchedregions, the resulting material is then separated by size on denaturingpolylacrylamide gels to determine the site of mutation. See, e.g.Cotton, et al., 1988 Proc. Natl Acad Sci USA 85: 4397; Saleeba, et al.1992, Methods Enzymol. 217: 286-295. In an embodiment, the control DNAor RNA can be labeled for detection.

[0286] In still another embodiment, the mismatch cleavage reactionemploys one or more proteins that recognize mismatched base pairs indouble-stranded DNA (so called “DNA mismatch repair” enzymes) in definedsystems for detecting and mapping point mutations in NOVX cDNAs obtainedfrom samples of cells. For example, the mutY enzyme of E. coli cleaves Aat G/A mismatches and the thymidine DNA glycosylase from HeLa cellscleaves T at G/T mismatches. See, e.g. Hsu, et al., 1994, Carcinogenesis15: 1657-1662. According to an exemplary embodiment, a probe based on aNOVX sequence, e.g. a wild-type NOVX sequence, is hybridized to a cDNAor other DNA product from a test cell(s). The duplex is treated with aDNA mismatch repair enzyme, and the cleavage products if any, can bedetected from electrophoresis protocols or the like. See e.g. U.S. Pat.No. 5,459,039.

[0287] In other embodiments, alterations in electrophoretic mobilitywill be used to identify mutations in NOVX genes. For example, singlestrand conformation polymorphism (SSCP) may be used to detectdifferences in electrophoretic mobility between mutant and wild typenucleic acids. See, e.g. Orita, et al., 1989, Proc. Natl. Acad. Sci.USA: 86: 2766; Cotton, 1993, Mutat. Res. 285: 125-144; Hayashi, 1992,Genet. Anal. Tech. Appl. 9: 73-79. Single-stranded DNA fragments ofsample and control NOVX nucleic acids will be denatured and allowed torenature. The secondary structure of single-stranded nucleic acidsvaries according to sequence, the resulting alteration inelectrophoretic mobility enables the detection of even a single basechange. The DNA fragments may be labeled or detected with labeledprobes. The sensitivity of the assay may be enhanced by using RNA(rather than DNA), in which the secondary structure is more sensitive toa change in sequence. In one embodiment, the subject method utilizesheteroduplex analysis to separate double stranded heteroduplex moleculeson the basis of changes in electrophoretic mobility. See. e.g. Keen, etal., 1991, Trends Genet 7: 5.

[0288] In yet another embodiment, the movement of mutant or wild-typefragments in polyacrylamide gels containing a gradient of denaturant isassayed using denaturing gradient gel electrophoresis (DGGE). See, e.g.Myers, et al. 1985, Nature 313: 495. When DGGE is used as the method ofanalysis. DNA will be modified to insure that it does not completelydenature, for example by adding a GC clamp of approximately 40 bp ofhigh-melting GC-rich DNA by PCR. In a further embodiment, a temperaturegradient is used in place of a denaturing gradient to identifydifferences in the mobility of control and sample DNA. See, e.g.,Rosenbaum and Reissner, 1987, Biophys Chem. 265: 12753.

[0289] Examples of other techniques for detecting point mutationsinclude, but are not limited to, selective oligonucleotidehybridization, selective amplification, or selective primer extension.For example, oligonucleotide primers may be prepared in which the knownmutation is placed centrally and then hybridized to target DNA underconditions that permit hybridization only if a perfect match is found.See, e.g. Saiki, et al., 1986, Nature 324: 163; Saiki, et al., 1989,Proc. Natl Acad Sci. USA 86: 6230. Such allele specific oligonucleotidesare hybridized to PCR amplified target DNA or a number of differentmutations when the oligonucleotides are attached to the hybridizingmembrane and hybridized with labeled target DNA.

[0290] Alternatively allele specific amplification technology thatdepends on selective PCR amplification may be used in conjunction withthe instant invention. Oligonucleotides used as primers for specificamplification may carry the mutation of interest in the center of themolecule (so that amplification depends on differential hybridization;see, e.g., Gibbs, et al., 1989, Nucl Acids Res 17: 2437-2448) or at theextreme 3′-terminus of one primer where, under appropriate conditions,mismatch can prevent, or reduce polymerase extension (see, e.g.,Prossner, 1993, Tibtech, 11: 238). In addition it may be desirable tointroduce a novel restriction site in the region of the mutation tocreate cleavage-based detection. See, e.g., Gasparini, et al., 1992,Mol. Cell Probes 6: 1. It is anticipated that in certain embodimentsamplification may also be performed using Taq ligase for amplification.See, e.g., Barany, 1991, Proc. Natl. Acad. Sci. USA 88: 189. In suchcases, ligation will occur only if there is a perfect match at the3′-terminus of the 5′ sequence, making it possible to detect thepresence of a known mutation at a specific site by looking for thepresence or absence of amplification.

[0291] The methods described herein may be performed, for example, byutilizing pre-packaged diagnostic kits comprising at least one probenucleic acid or antibody reagent described herein, which may beconveniently used, e.g. in clinical settings to diagnose patientsexhibiting symptoms or family history of a disease or illness involvinga NOVX gene.

[0292] Furthermore, any cell type or tissue, preferably peripheral bloodleukocytes, in which NOVX is expressed may be utilized in the prognosticassays described herein. However, any biological sample containingnucleated cells may be used, including, for example, buccal mucosalcells.

[0293] Pharmacogenomics

[0294] Agents, or modulators that have a stimulatory or inhibitoryeffect on NOVX activity (e.g. NOVX gene expression), as identified by ascreening assay described herein can be administered to individuals totreat (prophylactically or therapeutically) disorders. The disordersinclude but are not limited to, e.g., those diseases, disorders andconditions listed above, and more particularly include those diseases,disorders, or conditions associated with homologs of a NOVX protein,such as those summarized in Table A.

[0295] In conjunction with such treatment, the pharmacogenomics (i.e.the study of the relationship between an individual's genotype and thatindividual's response to a foreign compound or drug) of the individualmay be considered. Differences in metabolism of therapeutics can lead tosevere toxicity or therapeutic failure by altering the relation betweendose and blood concentration of the pharmacologically active drug. Thus,the pharmacogenomics of the individual permits the selection ofeffective agents (e.g., drugs) for prophylactic or therapeutictreatments based on a consideration of the individual's genotype. Suchpharmacogenomics can further be used to determine appropriate dosagesand therapeutic regimens. Accordingly, the activity of NOVX protein,expression of NOVX nucleic acid, or mutation content of NOVX genes in anindividual can be determined to thereby select appropriate agent(s) fortherapeutic or prophylactic treatment of the individual.

[0296] Pharmacogenomics deals with clinically significant hereditary,variations in the response to drugs due to altered drug disposition andabnormal action in affected persons. See e.g. Eichelbaum, 1996, Clin.Exp. Pharmacol Physiol. 23: 983-985; Linder, 1997, Clin Chem., 43:254-266. In general, two types of pharmacogenetic conditions can bedifferentiated. Genetic conditions transmitted as a single factoraltering the way drugs act on the body (altered drug action) or geneticconditions transmitted as single factors altering the way the body actson drugs (altered drug metabolism). These pharmacogenetic conditions canoccur either as rare defects or as polymorphisms. For example,glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commoninherited enzymopathy in which the main clinical complication ishemolysis after ingestion of oxidant drugs (anti-malarials,sulfonamides, analgesics, nitrofurans) and consumption of fava beans.

[0297] As an illustrative embodiment, the activity of drug metabolizingenzymes is a major determinant of both the intensity and duration ofdrug action. The discovery of genetic polymorphisms of drug metabolizingenzymes (e.g. N-acetyltransferase 2 (NAT 2) and cytochrome pregnancyzone protein precursor enzymes CYP2D6 and CYP2C19) has provided anexplanation as to why some patients do not obtain the expected drugeffects or show exaggerated drug response and serious toxicity aftertaking the standard and safe dose of a drug. These polymorphisms areexpressed in two phenotypes in the population, the extensive metabolizer(EM) and poor metabolizer (PM). The prevalence of PM is different amongdifferent populations. For example, the gene coding for CYP2D6 is highlypolymorphic and several mutations have been identified in PM, which alllead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6and CYP2C19 quite frequently experience exaggerated drug response andside effects when then receive standard doses. If a metabolite is theactive therapeutic moiety, PM show no therapeutic response, asdemonstrated for the analgesic effect of codeine mediated by itsCYP2D6-formed metabolite morphine. At the other extreme are the socalled ultra-rapid metabolizers who do not respond to standard doses.Recently, the molecular basis of ultra-rapid metabolism has beenidentified to be due to CYP2D6 gene amplification.

[0298] Thus, the activity of NOVX protein, expression of NOVX nucleicacid, or mutation content of NOVX genes in an individual can bedetermined to thereby select appropriate agent(s) for therapeutic orprophylactic treatment of the individual. In addition, pharmacogeneticstudies can be used to apply genotyping of polymorphic alleles encodingdrug-metabolizing enzymes to the identification of an individual's drugresponsiveness phenotype. This knowledge, when applied to dosing or drugselection, can avoid adverse reactions or therapeutic failure and thusenhance therapeutic or prophylactic efficiency when treating a subjectwith a NOVX modulator, such as a modulator identified by one of theexemplary screening assays described herein.

[0299] Monitoring of Effects During Clinical Trials

[0300] Monitoring the influence of agents (e.g. drugs, compounds) on theexpression or activity of NOVX (e.g. the ability to modulate aberrantcell proliferation and/or differentiation) can be applied not only inbasic drug screening, but also in clinical trials. For example, theeffectiveness of an agent determined by a screening assay as describedherein to increase NOVX gene expression, protein levels, or upregulateNOVX activity, can be monitored in clinical trails of subjectsexhibiting decreased NOVX gene expression, protein levels, ordownregulated NOVX activity. Alternatively, the effectiveness of anagent determined by a screening assay to decrease NOVX gene expression,protein levels, or downregulate NOVX activity, can be monitored inclinical trails of subjects exhibiting increased NOVX gene expression,protein levels, or upregulated NOVX activity. In such clinical trials,the expression or activity of NOVX and, preferably, other genes thathave been implicated in, for example, a cellular proliferation or immunedisorder can be used as a “read out” or markers of the immuneresponsiveness of a particular cell.

[0301] By way of example, and not of limitation, genes, including NOVX,that are modulated in cells by treatment with an agent (e.g., compound,drug or small molecule) that modulates NOVX activity (e.g., identifiedin a screening assay as described herein) can be identified. Thus, tostudy the effect of agents on cellular proliferation disorders, forexample, in a clinical trial, cells can be isolated and RNA prepared andanalyzed for the levels of expression of NOVX and other genes implicatedin the disorder. The levels of gene expression (i.e., a gene expressionpattern) can be quantified by Northern blot analysis or RT-PCR, asdescribed herein, or alternatively by measuring the amount of proteinproduced, by one of the methods as described herein, or by measuring thelevels of activity of NOVX or other genes. In this manner, the geneexpression pattern can serve as a marker, indicative of thephysiological response of the cells to the agent. Accordingly, thisresponse state may be determined before, and at various points during,treatment of the individual with the agent.

[0302] In one embodiment, the invention provides a method for monitoringthe effectiveness of treatment of a subject with an agent (e.g., anagonist, antagonist, protein, peptide, peptidomimetic, nucleic acid,small molecule, or other drug candidate identified by the screeningassays described herein) comprising the steps of (i) obtaining apre-administration sample from a subject prior to administration of theagent; (ii) detecting the level of expression of a NOVX protein, mRNA,or genomic DNA in the preadministration sample; (iii) obtaining one ormore post-administration samples from the subject; (iv) detecting thelevel of expression or activity of the NOVX protein, mRNA, or genomicDNA in the post-administration samples; (v) comparing the level ofexpression or activity of the NOVX protein, mRNA, or genomic DNA in thepre-administration sample with the NOVX protein, mRNA, or genomic DNA inthe post administration sample or samples; and (vi) altering theadministration of the agent to the subject accordingly. For example,increased administration of the agent may be desirable to increase theexpression or activity of NOVX to higher levels than detected, i.e., toincrease the effectiveness of the agent. Alternatively, decreasedadministration of the agent may be desirable to decrease expression oractivity of NOVX to lover levels than detected, i.e., to decrease theeffectiveness of the agent.

[0303] Methods of Treatment

[0304] The invention provides for both prophylactic and therapeuticmethods of treating a subject at risk of (or susceptible to) a disorderor having a disorder associated with aberrant NOVX expression oractivity. The disorders include but are not limited to e.g., thosediseases, disorders and conditions listed above, and more particularlyinclude those diseases, disorders, or conditions associated withhomologs of a NOVX protein, such as those summarized in Table A.

[0305] These methods of treatment will be discussed more fully, below.

[0306] Diseases and Disorders

[0307] Diseases and disorders that are characterized by increased(relative to a subject not suffering from the disease or disorder)levels or biological activity may be treated with Therapeutics thatantagonize (i.e., reduce or inhibit) activity. Therapeutics thatantagonize activity may be administered in a therapeutic or prophylacticmanner. Therapeutics that may be utilized include, but are not limitedto: (i) an aforementioned peptide, or analogs, derivatives, fragments orhomologs thereof; (ii) antibodies to an aforementioned peptide; (iii)nucleic acids encoding an aforementioned peptide; (iv) administration ofantisense nucleic acid and nucleic acids that are “dysfunctional” (i.e.due to a heterologous insertion within the coding sequences of codingsequences to an aforementioned peptide) that are utilized to “knockout”endogenous function of an aforementioned peptide by homologousrecombination (see, e.g., Capecchi, 1989, Science 244: 1288-1292); or(v) modulators (i.e., inhibitors, agonists and antagonists includingadditional peptide mimetic of the invention or antibodies specific to apeptide of the invention) that alter the interaction between anaforementioned peptide and its binding partner.

[0308] Diseases and disorders that are characterized by decreased(relative to a subject not suffering from the disease or disorder)levels or biological activity may be treated with Therapeutics thatincrease (i.e. are agonists to) activity. Therapeutics that upregulateactivity may be administered in a therapeutic or prophylactic manner.Therapeutics that may be utilized include, but are not limited to, anaforementioned peptide, or analogs, derivatives, fragments or homologsthereof; or an agonist that increases bioavailability.

[0309] Increased or decreased levels can be readily detected byquantifying peptide and/or RNA, by obtaining a patient tissue sample(e.g. from biopsy tissue) and assaying it in vitro for RNA or peptidelevels, structure and/or activity of the expressed peptides (or mRNAs ofan aforementioned peptide). Methods that are well-known within the artinclude, but are not limited to, immunoassays (e.g. by Western blotanalysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS)polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/orhybridization assays to detect expression of mRNAs (e.g., Northernassays, dot blots, in situ hybridization, and the like).

[0310] Prophylactic Methods

[0311] In one aspect, the invention provides a method for preventing, ina subject, a disease or condition associated with an aberrant NOVXexpression or activity, by administering to the subject an agent thatmodulates NOVX expression or at least one NOVX activity. Subjects atrisk for a disease that is caused or contributed to by aberrant NOVXexpression or activity can be identified by, for example, any or acombination of diagnostic or prognostic assays as described herein.Administration of a prophylactic agent can occur prior to themanifestation of symptoms characteristic of the NOVX aberrancy, suchthat a disease or disorder is prevented or, alternatively, delayed inits progression. Depending upon the type of NOVX aberrancy, for example,a NOVX agonist or NOVX antagonist agent can be used for treating thesubject. The appropriate agent can be determined based on screeningassays described herein. The prophylactic methods of the invention arefurther discussed in the following subsections.

[0312] Therapeutic Methods

[0313] Another aspect of the invention pertains to methods of modulatingNOVX expression or activity for therapeutic purposes. The modulatorymethod of the invention involves contacting a cell with an agent thatmodulates one or more of the activities of NOVX protein activityassociated with the cell. An agent that modulates NOVX protein activitycan be an agent as described herein, such as a nucleic acid or aprotein, a naturally-occurring cognate ligand of a NOVX protein, apeptide, a NOVX peptidomimetic, or other small molecule. In oneembodiment, the agent stimulates one or more NOVX protein activity.Examples of such stimulatory agents include active NOVX protein and anucleic acid molecule encoding NOVX that has been introduced into thecell. In another embodiment, the agent inhibits one or more NOVX proteinactivity. Examples of such inhibitory agents include antisense NOVXnucleic acid molecules and anti-NOVX antibodies. These modulatorymethods can be performed in vitro (e.g., by culturing the cell with theagent) or, alternatively, in vivo (e.g. by administering the agent to asubject). As such, the invention provides methods of treating anindividual afflicted with a disease or disorder characterized byaberrant expression or activity of a NOVX protein or nucleic acidmolecule. In one embodiment, the method involves administering an agent(e.g. an agent identified by a screening assay described herein), orcombination of agents that modulates (e.g., up-regulates ordown-regulates) NOVX expression or activity. In another embodiment, themethod involves administering a NOVX protein or nucleic acid molecule astherapy to compensate for reduced or aberrant NOVX expression oractivity.

[0314] Stimulation of NOVX activity is desirable in situations in whichNOVX is abnormally downregulated and/or in which increased NOVX activityis likely to have a beneficial effect. One example of such a situationis where a subject has a disorder characterized by aberrant cellproliferation and/or differentiation (e.g. cancer or immune associateddisorders). Another example of such a situation is where the subject hasa gestational disease (e.g., preclampsia).

[0315] Determination of the Biological Effect of the Therapeutic

[0316] In various embodiments of the invention, suitable in vitro or invivo assays are performed to determine the effect of a specificTherapeutic and whether its administration is indicated for treatment ofthe affected tissue.

[0317] In various specific embodiments, in vitro assays may be performedwith representative cells of the type(s) involved in the patient'sdisorder, to determine if a given Therapeutic exerts the desired effectupon the cell type(s). Compounds for use in therapy may be tested insuitable animal model systems including, but not limited to rats, mice,chicken, cows, monkeys, rabbits, and the like, prior to testing in humansubjects. Similarly, for in vivo testing, any of the animal model systemknown in the art may be used prior to administration to human subjects.

[0318] Prophylactic and Therapeutic Uses of the Compositions of theInvention

[0319] The NOVX nucleic acids and proteins of the invention are usefulin potential prophylactic and therapeutic applications implicated in avariety of disorders. The disorders include but are not limited to,e.g., those diseases, disorders and conditions listed above, and moreparticularly include those diseases, disorders, or conditions associatedwith homologs of a NOVX protein, such as those summarized in Table A.

[0320] As an example, a cDNA encoding the NOVX protein of the inventionmay be useful in gene therapy, and the protein may be useful whenadministered to a subject in need thereof. By way of non-limitingexample, the compositions of the invention will have efficacy fortreatment of patients suffering from diseases, disorders, conditions andthe like, including but not limited to those listed herein.

[0321] Both the novel nucleic acid encoding the NOVX protein, and theNOVX protein of the invention, or fragments thereof, may also be usefulin diagnostic applications, wherein the presence or amount of thenucleic acid or the protein are to be assessed. A further use could beas an anti-bacterial molecule (i.e., some peptides have been found topossess anti-bacterial properties). These materials are further usefulin the generation of antibodies, which immunospecifically-bind to thenovel substances of the invention for use in therapeutic or diagnosticmethods.

[0322] The invention will be further described in the followingexamples, which do not limit the scope of the invention described in theclaims.

EXAMPLES Example A Polynucleotide and Polypeptide Sequences, andHomology Data Example 1

[0323] The NOV1 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 1A. TABLE 1A NOV1 SequnenceAnalysis SEQ ID NO:1 829 bp NOV1a.GTCCTTGGAGGCCAGAGGGGACTCTGAGCATCGGAAAGCAGG ATGCCTGGTTTGCTTT CG102071-01DNA Sequence TATGTGAACCGACAGAGCTTTACAACATCCTGAATCAGGCCACAAAACTCTCCAGATTAACAGACCCCAACTATCTCTGTTTATTGGATGTCCGTTCCAAATGGGAGTATGACGAAAGCCATGTGATCACTGCCCTTCGAGTGAAGAAGAAAAATAATGAATATCTTCTCCCGGAATCTGTGGACCTGGAGTGTGTGAAGTACTGCGTGGTGTATGATAACAACAGCAGCACCCTGGAGATACTCTTAAAAGATGATGATGATGATTCAGACTCTGATGGTGATGGCAAAGGAACTGGATGCATTTCAGCCATACCCCATGA AATCGTGCCAGGGAAGGTCTTCGTTGGCAATTTCAGTCAAGCCTGTGACCCCAAGATTCAGAAGGACTTGAAAATCAAAGCCCATGTCAATGTCTCCATGGATACAGGGCCCTTTTTTGCAGGCGATGCTGACAAGCTTCTGCACATCCGGATAGAAGATTCCCCCGAACCCCAGATTCTTCCCTTCTTACGCCACATGTGTCACTTCATTGGGTATCAGCCGCAGTTGTGCCGCCATCATAGCCTACCTCATGTATAGTAACGAGCAGACCTTGCAGAGGTCCTGGGCCTATGTCAAGAAGTGCAAAAACAACATGTGTCCAAATCGGGGATTGGTGAGCCAGCTGCTGGAATGGGAGAAGACTATCCTTGGAGATTCCATCACAAACATCATGGATCCGCTCTACTGATCTTCTCCGAGGCCCACCGAAGGGTACTGAAGAGCCTC ORf Start: ATG at 43 ORf Stop: IGA at 379 SEQ ID NO:2112 aa MW at 12612.0kD NOV1a.MPGLLLCEPTELYNILNQATKLSRLTDPNYLCLLDVRSKWEYDESHVITALRVKKKNN CG102071-01Protein Sequence EYLLPESVDLECVKYCVVYDNNSSTLEILLKDDDDDSDSDGDGKGTGCISAIPH

[0324] Further analysis of the NOV1a protein yielded the followingproperties shown in Table 1B. TABLE 1B Protein Sequence Properties NOV1aPSort 0.4500 probability located in cytoplasm: 0.3000 analysis:probability located in microbody (peroxisome); 0.1000 probabilitylocated in mitochondrial matrix space: 0.1000 probability located inlysosome (lumen) SignalP No Known Signal Sequence Predicted analysis:

[0325] A search of the NOV1a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table1C. TABLE 1C Geneseq Results for NOV1a NOV1a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier +190, Date] Residues Region Value AAY44241Human cell signalling protein-4-   1..102 102/102 (100%) 1e−55 Homosapiens. 313 aa.   1..102 102/102 (100%) [WO9958558-A2. 18-NOV-1999]AAGO1344 Human secreted protein. SEQ ID   1..59  55/59 (93%) 2e−26NO:5425-Homo sapiens. 125 aa.   1..59  57/59 (96%)[EP1033401-A2.06-SEP-2000] AAM91270 Human immune/haematopoictic   1..56 54/56 (96%) 1e−25 antigen SEQ ID NO:18863-Homo   7..62  55/56 (97%)sapiens. 123 aa. ]WO200157182- A2.09-AUG-2001] AAY07958 Human secretedprotein fragment  71..102  32/32 (100%) 3e−12 #2 encoded from gene6-Homo  34..65  32/32 (100%) sapiens. 276 aa. [WO9918208-A1.15-APR-1999] AAY68782 Amino acid sequence ot a human  17..112  24/103(23%) 1.7 phosphorylation effector PHSP-14- 182..284  46/103 (44%) Homosapiens, 416 aa. [WO200006728-A2. 10-FEB-2000]

[0326] In a BLAST search of public sequence datbases, the NOV1a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 1D. TABLE 1D Public BLASTP Results for NOV1a NOV1a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9Y6J8 Map kinasephosphatase-like  1 . . . 102 102/102 (100%)  2e−55 protein MK-STYX -Homo sapiens  1 . . . 102 102/102 (100%)  (Human). 313 aa. Q9DAR2 Adultmale testis cDNA. RIKEN 1 . . . 98 66/98 (67%)  2e−35 full-lengthenriched library. 1 . . . 98 86/98 (87%)  clone: 1700001J05. full insertsequence - Mus musculus (Mouse), 321 aa. Q9UBP1 MAP kinasephosphatase-like 46 . . . 112 67/67 (100%) 1e−33 protein MK-STYX - Homosapiens 1 . . . 67 67/67 (100%) (Human). 67 aa (fragment). Q9UK07 Mapkinase phosphatase-like 46 . . . 102 57/57 (100%) 6e−27 proteinMK-STYX - Homo sapiens 1 . . . 57 57/57 (100%) (Human). 221 aa(fragment). Q8XMD0 Hypothetical protein CPE0759 - 15 . . . 98  27/87(31%)  0.041 Clostridium perfringens. 399 aa. 296 . . . 380  46/87(52%) 

[0327] PFam analysis predicts that the NOV1a protein contains thedomains shown in the Table 1E. TABLE 1E Domain Analysis of NOV1a PfamNOV1a Match Identities/ Expect Value Domain Region Similarities for theMatched Region

Example 2

[0328] The NOV2 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 2A. TABLE 2A NOV2 SequenceAnalysis SEQ ID NO:3 1188 bp NOV2a.AGTGATGGCTTGTGGATTCAAGCCTAGGTTTGACAGATCTGGAATGTGTGCTCCTATT CG112767-01DNA Sequence CCTCCGCAGTCTGGCCTGTCTGCTTTCTGTCTTCTTTGCCAGCAATGTCCAGGCACTGTAAGGTGGGCCGTTAGCTTCCTGGGTTCAGGTAAATGTCTTCCAGTAACCCCTGCTTCCCCTGCTCCCCGACAGGTAAGTTCGAGGATCGGGAAGACCACGTCCCCAAGTTGGAGCAAATAAACAGCACGAGGATCCTGAGCAGCCAGAACTTCACCCTCACCAAGAAGGAGCTGCTGAGCACAGAGCTGCTGCTCCTGGAGGCCTTCAGCTGGAACCTCTGCCTGCCCACGCCTCCCCACTTCCTGGACTACTACCTCTTGGCCTCCGTCAGCCAGAAGGACCACCACTGCCACACCTGGCCCACCACCTGCCCCCCGAAGACCAAAGAGTGCCTCAAGGACTATGCCCATTACTTCCTAGAGGTCACCCTGCAAGTCGCTGCGGCCTGTGTTGGGGCCTCCAGGATTTGCCTGCAGCTTTCTCCCTACTGGACCAGAGACCTGCAGAGGATCTCAAGCTATTCCCTGGAGCACCTCAGCACGTGTATTGAAATCCTGCTGGTGGTGTATGACAACGTCCTCAAGGATGCCGTAGCCGTCAAGAGCCAGGCCTTGGCAATGGTGCCCGGCACACCCCCCACCCCCACTCAAGTGCTGTTCCAGCCACCAGCCTACCCGGCCCTCGGCCAGCCAGCGACCACCCTGGCACAGTTCCAGACCCCCGTGCAGGACCTATGCTTGGCCTATCGGGACTCCTTGCAGGCCCACCGTTCAGGGAGCCTGCTCTCGGGGAGTACAGGCTCATCCCTCCACACCCCGTACCAACCGCTGCAGCCCTTGGATATGTGTCCCGTGCCCGTCCCTGCATCCCTTAGCATGCATATGGCCATTGCAGCTGAGCCCAGGCACTGCCTCGCCACCACCTATGGAAGCAGCTACTTCAGTGGGAGCCACATGTTCCCCACCGGCTGCTTTGACAGATAG GCCACCTCCAGACCTCACGAGGAAGCCTTGGAGATGTGGGCAGAGGAAGAGGACACTGAAGAGGAGAGCTCAGCCAAGTGAGGCAGCAGGAGGCCATCCCTGAAGAGCCTTGGAACGTGGAGGGTCTGTGCTCCTTTTAAATAAAAC ORF Start: ATG at 151 ORF Stop: TAG at 1039SEQ ID NO:4 296 aa MW at 32755.1kD NOV2a.MSSSNPCFPCSPTGKFEDREDHVPKLEQINSTRILSSQNFTLTKKELLSTELLLLEAF CG112767-01Protein SequenceSWNLCLPTPAHFLDYYLLASVSQKDHHCHTWPTTCPRKTKECLKEYAHYFLEVTLQVAAACVGASRICLQLSPYWTRDLQRISSYSLEHLSTCIETLLVVYDNVLKDAVAVKSQALAMVPGTPPTPTQVLFQPPAYPALGQPATTLAQFQTPVQDLCLAYRDSLQAHRSGSLLSGSTGSSLHTPYQPLQPLDMCPVPVPASLSMHMAIAAEPRHCLATTYGSSYFSGSHMFP TGCFDR SEQ IDNO:5 1015 bp NOV2b. GTTAGCTTCCTGGGTTCAGGTAAATGTCTTCCAGTAACCCCTGCTTCCCCTGCTCCCC CG112767-02 DNA SequenceGACAGGTAAGTTCGAGGATCGGGAAGACCACGTCCCCAAGTTGGAGCAAATAAACAGCACGAGGATCCTGAGCAGCCAGAACTTCACCCTCACCAAGAAGGAGCTGCTGAGCACAGAGCTGCTGCTCCTGGAGGCCTTCAGCTGGAACCTCTGCCTGCCCACGCCTGCCCACTTCCTGGACTACTACCTCTTGGCCTCCGTCAGCCAGAAGGACCACCACTGCCACACCTGGCCCACCACCTGCCCCCGCAAGACCAAAGAGTGCCTCAAGGAGTATGCCCATTACTTCCTAGAGGTCACCCTGCAAGATCACATATTCTACAAATTCCAGCCTTCTGTGGTCGCTGCGGCCTGTGTTGGGGCCTCCAGGATTTGCCTGCAGCTTTCTCCCTACTGGACCAGAGACCTGCAGAGGATCTCAAGCTATTCCCTGGACCACCTCAGCACGTGTATTGAAATCCTGCTGGTAGTGTATGACAACGTCCTCAAGGATGCCGTAGCCGTCAAGAGCCAGGCCTTGGCAATGGTGCCCGGCACACCCCCCACCCCCACTCAAGTGCTGTTCCAGCCACCAGCCTACCCGGCCCTCGGCCAGCCAGCGACCACCCTGGCACAGTTCCAGACCCCCGTGCAGGACCTATGCTTGGCCTATCGGGACTCCTTGCAGGCCCACCGTTCAGGGAGCCTGCTCTCGGGGAGTACAGGCTCATCCCTCCACACCCCGTACCAACCGCTGCAGCCCTTGGATATGTGTCCCGTGCCCGTCCCTGCATCCCTTAGCATGCATATGGCCATTGCAGCTGAGCCCAGGCACTGCCTCGCCACCACCTATGGAAGCAGCTACTTCAGTGGGAGCCACATGTTCCCCACCGGCTGCTTTGACAGATATAG GCCACCTCCAGACCTCACGAGGAAGCCTTGGAGATGTGGGCAGAGGAAGAGGACACTGAAGAGGAGAG ORF Start: ATG at 24 ORF Stop: TAG at 945SEQ ID NO:6 307 aa MW at 34117.7kD NOV2b.MSSSNPCFPCSPTGKFEDREDHVPKLEQINSTRILSSQNFTLTKKELLSTELLLLEAF CG112767-02Protein SequenceSWNLCLPTPAHRLDYYLLASVSQKDHHCHTWRTTCPRKTKECLKEYAHYFLEVTLQDHIFYKFQPSVVAAACVGASRICLQLSPYWTRDLQRISSYSLEHLSTCIEILLVVYDNVLKDAVAVKSQALAMVPGTPPTPTQVLFQPPAYPALGQPATTLAQFQTPVQDLCLAYRDSLQAHRSGSLLSGSTGSSLHTPYQPLQPLDMCPVPVPASLSMHMAIAAEPRHCLATTYGSSYFSGSHMFPTGCFDR

[0329] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 2B. TABLE 2B Comparisonof NOV2a against NOV2b. Protein NOV2a Residues/ Identities/ SequenceMatch Residues Similarities for the Matched Region NOV2b 1 . . . 296267/307 (86%) 1 . . . 307 267/307 (86%)

[0330] Further analysis of the NOV2a protein yielded the followingproperties shown in Table 2C. TABLE 2C Protein Sequence Properties NOV2aPSort 0.6500 probability located in cytoplasm; 0.1000 analysis:probability located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen): 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0331] A search of the NOV2a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table2D. TABLE 2D Geneseq Results for NOV2a NOV2a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAE18955 Humancell cycle protein and 15..296 281/293 (95%) e−164 mitosts-associatedmolecule 59..351 281/293 (95%) (CCPMAM-3)-Homo sapiens, 351aa.[WO200208255-A2, 31-JAN- 2002] AAB95737 Human protein sequence SEQ ID176..296 121/121 (100%) 2e−68 NO:18627-Homo sapiens, 121 aa.  1..121121/121 (1000o) [EP1074617-A2.07-FEB-2001] AAB93306 Human proteinsequence SEQ ID 51..296 99/254 (38%) 3e−35 NO:l2379-Homo sapiens, 242aa.  2..242 133/254 (51%) [EP1074617-A2.07-FEB-2001] AAB40749 Human OREX0RF513 polypeptide 15..45 31/31 (100%) 4e−10 sequence SEQ IDNO:1026-Homo 95..125 31/31 (100%) sapiens. 125 aa. [WO200058473- A2.05-OCT-2000] AAG29317 Arabidopsis thaliana protein 44.161 32/119 (26%)0.002 fragment SEQ ID NO: 34860- 61..174 57/119 (47%) Arabidopsisthaliana. 209 aa. [EP1033405-A2. 06-SEP-2000

[0332] In a BLAST search of public sequence datbases, the NOV2a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 2E TABLE 2E Public BLASTP Results for NOV2a NOV2a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9H7W8 CDNAFLJ14166 fis. clone 176 . . . 296   121/121 (100%) 5e−68 NT2RP1000796(Hypothetical 12.9  1 . . . 121  121/121 (100%) kDa protein) - Homosapiens (Human), 121 aa. Q96LF7 BA690P14.1 (Novel cyclin 15 . . . 296118/290 (40%) 2e−46 (Contains FLJ10895)) - Homo 62 . . . 338 159/290(54%) sapiens (Human). 338 aa (fragment). Q9NV69 CDNA FLJ10895 fis.clone 51 . . . 296  99/254 (38%) 8e−35 NT2RP4002905 - Homo sapiens  2 .. . 242 133/254 (51%) (Human), 242 aa. Q8T2F2 Hypothetical 81.0 kDaprotein - 11 . . . 167  39/175 (22%) 1e−06 Dictyostelium discoideum(Slime 517 . . . 677   75/175 (42%) mold). 694 aa. P93557 Mitoticcyclin - Sesbania rostrata. 28 . . . 162  40/146 (27%) 2e−06 445 aa. 283. . . 409   65/146 (44%)

[0333] PFam analysis predicts that the NOV2a protein contains thedomains shown in the Table 2F. TABLE 2F Domain Analysis of NOV2aIdentities/ NOV2a Match Similarities Expect Pfam Domain Region for theMatched Region Value cyclin_C 65 . . . 204 32/166 (19%) 0.01 94/166(57%)

Example 3

[0334] The NOV3 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 3A TABLE 3A NOV3 SequenceAnalysis SEQ ID NO:7 1534 bp NOV3a.AAGCATGGTTAAATCTGGTAGATGGAGAGCTCAGGAAAAGCGGCCATGAGCTTTCAGC CC112776-01DNA Sequence ACAATTAGTCCTCACCCTTAGGGGACACCCTAAGGGAAGATGAGTCCCAGGACTAACCAGGGGTGTGGGCATCCCTGTGTTTAAAATTCCAG ATGGGCACCACACCTTCCAAACCGGACACTCCCTTAGATGTATCCTGAATAACTGGGACAAATTCGACCCTGAAACCTTAAAAAAAGAAGCAGCTAATTTTCTTCTGTACCACTGCCTGGCCACAGTATTCCTTACAAAATGGAGAAACTTGGCCCCCTGAGGGATGTATTAATTATAACACCCTTCTACAACTAGCTCTTTTCTGTAAGCAGGAAGGTAAATGGAGTGAAGTCCCTTACGTACAGGCTTTCTTTGCCCTTCTTGACAATACTGCCCTGTGCCAAGCCTGCGAGCTTTGCCCAAATGACAGAGGCCCACAATTACCTCCATATTCAGGGCCTCTTCCCTCAGCCCCACTCTCCTCCTGCACTGACTCTCCTCCATCTGGCCTCACTGAAGTGTTAAAGGCAAAATGGAAAGAGAACGTAAACTCCGAGAGCCAGGCACCCGAACTATGTCCCTTACAAACAGTAGGAGGAGAATTTGGGCGCATTCACATGCATGCCCCCTTCTCACTCTCAAATTTAAAACAAATAAAGGCAGATTTAGGGAAATTCTTGGATGATCCTGATAACCATATACATGTCCTGCAAGGATTAGAGCAGTCCTTTGATCTAACATGGAGAGATATCATGTTACTTCTTGATCAGACCTTAAGTCCTACTGAAAAAAAAGCAGCTTTAGCAGCAGCCCAGCAATTTAGGGATCGATGGTACCTTGGCCAGGTAAACAATCCATTGATGGCCTTGGAGGAGAGGGAAAAATTGCCCACAGGGGAACAGGCAGTCCCCACTGTAAATCCTTATTGGGATACTGACTCAGATCATGGAGATTGGAGCCACAGGCATTTGCTAACTTGCATTTTAAAAGGGTTGAGGAAGACTAGGAGAAAGCCTATGAACTACTCAATGCTATCCACCATTACCCAGGGAAAAGAAGAAAATCCCTCAGCCTTTCTAGAAATGCTGCGGGAGGCTCTAAGAAGGCACACCCCCGTAACTCCGGATTCCCTGGAAGGCCAACTTATTCTAAAGGATAAACTTATCACCCTAAGAAGCGGCCGATATTGGGAGAAAACTCCAAAGGTCTGCCTTAGGCCCAGAACAAAGCTTGGAGGCATTATTAAACCTGCCAACCTCGTTGTTCTATAA CAGGGACCAAGAGGAACAGGCCAAAATGGAAAAGCAAGATAAGAGAAAGGCTGCAGCCTTAGTCTTGGCTCTCAGACAGGCAGACCTTGGTGGCTCAGAGGGAACCAAAAGAGGAGCAGGCCAATTGCCTAGTAGGGCTTGTTATCAGTGCGGTTTGCAAGGACACTTTAAAAAAGATTGTCCAACTAGAAACAAACTGCCCCCTCGCCCATGTCCAATATGCCAAGGCAAT ORF Start: ATG at 151 ORF Stop: TAA at 1300SEQ ID NO:8 383 aa MW at 43317.3kD NOV3a.MGTTPSKPDTPLRCILNNWDKFDPETLKKKQLIFFCTTAWPQYSLQNGETWPPEGCIN CG112776-01Protein SequenceYNTLLQLALFCKQEGKWSEVPYVQAFFALLDNTALCQACELCPNDRGPQLPPYSGPLPSAPLSSCTDSPPSGLTEVLKAKWKENVNSESQAPELCPLQTVGGEFGRIHMHAPFSLSNLKQIKADLGKFLDDPDNHIHVLQGLEQSPDLTWRDIMLLLDQTLSPTEKKAALAAAQQFRDRWYLGQVNNPLMALEEREKLPTGEQAVPTVNPYWDTDSDHGDWSHRHLLTCILKGLRKTRRKPMNYSMLSTITQGKEENPSAFLEMLREALRRHTPVTPDSLEGQLILKDKLITLRSGRYWEKTPKVCLRPRTKLGGIIKPANLVVL

[0335] Further analysis of the NOV3a protein yielded the followingproperties shown in Table 3B. TABLE 3B Protein Sequence Properties NOV3aPSort 0.3000 probability located in nucleus: 0.1000 analysis:probability located in mitochondrial matrix space: 0.1000 probabilitylocated in lysosome (lumen): 0.0000 probability located in encloplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0336] A search of the NOV3a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table3C. TABLE 3C Geneseq Results for NOV3a NOV3a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAB07704Protein encoded by the endogenetic 1 . . . 350 227/354 (64%) e−131fragment of HERV-W - Homo 1 . . . 349 274/354 (77%) sapiens. 363 aa.[WO200043521- A2, 27 Jul. 2000] AAB07702 Protein encoded by theendogenetic 1 . . . 350 227/354 (64%) e−131 fragment of HERV-W - Homo 34. . . 382  274/354 (77%) sapiens. 409 aa. [WO200043521- A2, 27 Jul.2000] AAB07703 Protein encoded by the endogenetic 1 . . . 350 227/358(63%) e−128 fragment of HERV-W - Homo 14 . . . 366  274/358 (76%)sapiens, 393 aa. [WO200043521- A2. 27 Jul. 2000] AAB08194 Amino acidsequence of the MSRV- 1 . . . 350 223/354 (62%) e−126 1 RU5 region andgag region - 1 . . . 349 271/354 (75%) Multiple Sclerosis retrovirus 1.484 aa. [WO200047745-A1. 17 Aug. 2000] AAW99558 Protein encoded bypET21C-clone 2 12 . . . 350  219/343 (63%) e−124 from MSRV-1 - Multiplesclerosis 14 . . . 351  266/343 (76%) related virus type 1. 378 aa.[FR2765588-A1. 08 Jan. 1999]

[0337] In a BLAST search of public sequence datbases, the NOV3a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 3D. TABLE 3D Public BLASTP Results for NOV3a NOV3a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9NRZ4 Gag - Homosapiens (Human), 363 1 . . . 350 227/354 (64%)  e−131 aa. 1 . . . 349274/354 (77%) Q9PZ44 Gag polyprotein - multiple 12 . . . 350  219/343(63%)  e−123 sclerosis associated retrovirus 1 . . . 338 266/343 (76%)element. 352 aa (fragment). Q9PZ45 Gag polyprotein - multiple 1 . . .136  78/136 (57%) 3e−39 sclerosis associated retrovirus 1 . . . 135 91/136 (66%) element. 137 aa (fragment). Q9BRM8 Hypothetical 14.1 kDaprotein - 1 . . . 87   60/87 (68%) 5e−33 Homo sapiens (Human), 123 aa. 1. . . 87   74/87 (84%) O36448 Gag - Fowlpox virus (FPV), 499 10 . . .363  102/412 (24%) 3e−18 aa. 11 . . . 402  163/412 (38%)

[0338] PFam analysis predicts that the NOV3a protein contains thedomains shown in the Table 3E. TABLE 3E Domain Analysis of NOV3aIdentities/ Pfam NOV3a Match Similarities Domain Region for the MatchedRegion Expect Value Gag_p30 260 . . . 337 32/78 (41%) 1.3e−12 45/78(58%)

Example 4

[0339] The NOV4 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 4A. TABLE 4A NOV4 SequenceAnalysis SEQ ID NO:9 1287 bp NOV4a. GCCCTGATGGAGCACCTTGTTCCCACGGTGGACTATTACCCCGATAGGACGTACATCT CG122759-01 DNASequence TCACCTTTCTCCTGAGCTCCCGGGTCTTTATGCCCCCTCATGACCTGCTGGCCCGCGTGGGGCAGATCTGCGTGGAGCAGAAGCAGCAGCTGGGAACCGGGCCTGAAAAGCAGGCCAAGCTGAAGTCTTTCTCAGCCAAGATCGTGCAGCTCCTGAAGGAGTGGACCGAGGCCTTCCCCTATGACTTCCAGGATGAGAAGGCCATGGCCGAGCTGAAAGCCATCACACACCGTGTCACCCAGTGTGATGAGGAGAATGGCACAGTGAAGAAGGCCATTGCCCAGATGACACAGAGCCTGTTGCTCTCCTTGGCTGCCCCGAGCCAGCTCCAGGAACTGCGAGAGAAGCTCCGGCCACCGGCTGTAGACAAGGGGCCCATCCTCAAGACCAAGCCACCAGCCGCCCAGAAGGACATCCTGGGCGTGTGCTGCGACCCCCTGGTGCTGGCCCAGCAGCTGACTCACATTGAGCTGGACAGGGTCAGCAGCATTTACCCTGAGGACTTGATGCAGATCGTCAGCCACATGGACTCCTTGGACAACCACAGGTGCCGAGGGGACCTGACCAAGACCTACAGCCTGGAGGCCTATGACAACTGGTTCAACTGCCTGAGCATGCTGGTGGCCACTGAGGTGTGCCGGGTAGTGAAGAAGAAACACCGGACCCGCATGTTGGAGTTCTTCATTGATGTGGCCCGGGAGTGCTTCAACATCGGGAACTTCAACTCCATGATGGCCATCATCGCAGCTGGCATGAACCTCAGTCCTGTGGCAAGGCTGAAGAAAACTTGGTCCAAGGTCAAGACACCCAAGTTTGATGTCTTGGAGCATCACATGGACCCGTCCAGCAACTTCTGCAACTACCGTACAGCCCTGCAGGGGGCCACGCAGAGGTCCCAGATGGCCAACAGCAGCCGTGAAAAGATCGTCATCCCTGTGTTCAACCTCTTCGTTAAGGACATCTACTTCCTGCACAAAATCCATACCAACCACCTGCCCAACGGGCACATTAACTTTAAGCAGAAATTCTGGGAGATCTCCAGACAGATCCATGAGTTCATGACATGGACACAGGTAGAGTGTCCTTTCGAGAAGGACAAGAAGATTCAGAGTTACCTGCTCACGGCGCCCATCTACAGCGAGGAAGCTCTCTTCGTCGCCTCCTTTGAAAGTGAGGGTCCCGAGAACCACATGGAAAAAGACAGCTGGAAGACCCTCA GGTAG GACGGCORF Start: ATG at 7 ORF Stop: TAG at 1279 SEQ ID NO:10 424 aa MW at48967.1kD NOV4a.MEHLVPTVDYYPDRTYIFTFLLSSRVFMPPHDLLARVGQICVEQKQQLEAGPEKQAKL CG122759-01Protein SequenceKSFSAKIVQLLKEWTEAFPYDFQDEKAMAELKAITHRVTQCDEENGTVKKAIAQMTQSLLLSLAARSQLQELREKLRPPAVDKGPILKTKPPAAQKDILGVCCDPLVLAQQLTHIELDRVSSIYPEDLMQIVSHMDSLDNHRCRGDLTKTYSLEAYDNWFNCLSMLVATEVCRVVKKKHRTRMLEFFIDVARECFNIGNFNSMMAIIAAGMNLSPVARLKKTWSKVKTAKFDVLEHHMDPSSNFCNYRTALQGATQRSQMANSSREKIVIPVFNLFVKDIYFLHKIHTNHLPNGHTNFKQKFWEISRQIHEFMTWTQVECPFEKDKKIQSYLLTAPIYSEEALFVASFESEGPENHMEKDSWKTLR SEQ ID NO:11 1269 bp NOV4b. CTGATGGAGCACCTTGTTCCCACGGTGGACTATTACCCCGATAGGACGTACATCTTCA CG122759-02 DNASequence CCTTTCTCCTGAGCTCCCGGGTCTTTATGCCCCCTCATGACCTGCTGGCCCGCGTGGGGCAGATCTGCGTGGAGCAGAAGCAGCAGCTGGAAGCCGGGCCTGAAAAGGCCAAGCTGAAGTCTTTCTCAGCCAAGATCGTGCAGCTCCTGAAGGAGTGGACCGAGGCCTTCCCCTATGACTTCCAGGATGAGAAGGCCATGGCCGAGCTGAAAGCCATCACACACCGTGTCACCCAGTGTGATGAGGAGAATGGCACAGTGAGGAAGGCCATTGCCCAGATGACACAGAGCCTCTTGCTGTCCTTGGCTGCCCGGAGCCAGCTCCAGGAACTGCGAGAGAAGCTCCGGCCACCGGCTGTAGACAAGGGGCCCATCCTCAAGACCAAGCCACCAGCCGCCCAGAAGGACATCCTGGGCGTGTGCTGCGACCCCCTGGTGCTGGCCCAGCAGCTGACTCACATTGAGCTGGACAGGGTCAGCAGCATTTACCCTGAGGACTTGATGCAGATCGTCAGCCACATGGACTCCTTGGACAACCACAGGTGCCGAGGGGACCTGACCAAGACCTACAGCCTGGAGGCCTATGACAACTGGTTCAACTGCCTGAGCATGCAGGTGGCCACTGAGGTGTGCCGGGTGGTGAAGAAGAAACACCGGGCCCGCATGTTGGAGTTCTTCATTGATGTGGCCCGGGAGTGCTTCAACATCGGGAACTTCAACTCCATGATGGCCATCATCTCTGGCATGAACCTCAGTCCTGTGGCAAGGCTGAAGAAAACTTGGTCCAAGGTCAAGACAGCCAAGTTTGATGTCTTGGAGCATCACATGGACCCGTCCAGCAACTTCTGCAACTACCGTACAGCCCTGCAGGGGGCCACGCAGAGGTCCCAGATGGCCAACAGCAGCCGTGAAAAGATCGTCATCCCTGTGTTCAACCCCTTCGTTAAGGACATCTACTTCCTGCACAAAATCCATACCAACCACCTGCCCAACGGGCACATTAACTTTAAGAAATTCTGGGAGATCTCCAGACAGATCCATGAGTTCATGACATGGACACAGGTAGAGTGTCCTTTCGAGAAGGACAAGAAGATTCAGAGTTACCTGCTCACGGCGCCCATCTACAGCGAGGAAGCTCTCTTCGTCGCCTCCTTTGAAAGTGAGGGTCCCGAGAACCACATGGAAAAAGACAGCTGGAAGACCCTCAGGTAG ORF Start: ATG at 4ORF Stop: TAG at 1267 SEQ ID NO:12 421 aa MW at 48652.7kD NOV4b.MEHLVPTVDYYPDRTYIFTFLLSSRVFMPPHDLLARVGQICVEQKQQLEAGPEKAKLK CG122759-02Protein SequenceSFSAKIVQLLKEWTEAFPYDFQDEKAMAELKAITHRVTQCDEENGTVRKAIAQMTQSLLLSLAARSQLQELREKLRPPAVDKGPILKTKPPAAQKDILGVCCDRLVLAQQLTHIELDRVSSIYPEDLMQIVSHMDSLDNHRCRGDLTKTYSLEAYDNWFNCLSMQVATEVCRVVKKKHRARMLEFFIDVARECFNIGNFNSMMAIISGMNLSPVARLKKTWSKVKTAKFDVLEHHMDPSSNFCNYRTALQGATQRSQMANSSREKIVIPVFNPFVKDIYFLHKIHTNHLPNGHINFKKFWEISRQIHEFMTWTQVECPFEKDKKIQSYLLTAPIYSEEALFVASFESEGPENHMEKDSWKTLR

[0340] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 4B. TABLE 4B Comparisonof NOV4a against NOV4b. Protein NOV4a Residues/ Identities/ SequenceMatch Residues Similarities for the Matched Region NOV4b 1 . . . 424400/424 (94%) 1 . . . 421 402/424 (94%)

[0341] Further analysis of the NOV4a protein yielded the followingproperties shown in Table 4C. TABLE 4C Protein Sequence Properties NOV4aPSort 0.6000 probability located in nucleus; 0.3735 analysis:probability located in microbody (peroxisome); 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probability located inlysosome (lumen) SignalP No Known Signal Sequence Predicted analysis:

[0342] A search of the NOV4a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table4D. TABLE 4D Geneseq Results for NOV4a NOV4a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value ABB04984 Humannew ras guanine-nucleotide-   1..424 259/425 (60%) e−151 exchange factor1 SEQ ID NO:2-  47..466 333/425 (77%) Homo sapiens. 473 aa.[WO200185934-A1.15-NOV-2001] AAG67823 Human guanine-nucleotide releasing  1..424 258/425 (60%) e−150 factor 52 protein-Homo sapiens,  47..465331/425 (77%) 472 aa.[CN1297910-A. 06-JUN- 2001] AAB68566 HumanGTP-binding associated   1..424 239/426 (56%) e−131 protein #66-Homosapiens. 466 aa.  47..459 309/426 (72%) [WO200105970-A2.25-JAN-2001]AAU28253 Novel human secretory protein. Seq 194..424 213/232 (91%) e−120ID No 610-Homo sapiens. 237 aa.   1..230 218/232 (93%) [WO200166689-A2.13-SEP-2001] ABG23436 Novel human diagnostic protein 201..424 206/242(85%) e−112 #23427-Homo sapiens. 261 aa.  15..254 211/242 (87%)[WO200175067-A2. 11-OCT-2001]

[0343] In a BLAST search of public sequence datbases, the NOV4a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 4E TABLE 4E Public BLASTP Results for NOV4a NOV4a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q8TBF1 Similar toRIKEN cDNA 1 . . . 424 419/424 (98%) 0.0 6330404M18 gene - Homo sapiens1 . . . 421 421/424 (98%) (Human). 428 aa. Q9D3B6 6330404M18Rikprotein - Mus 1 . . . 424 398/424 (93%) 0.0 musculus (Mouse). 428 aa. 1. . . 421 410/424 (95%) Q96MY8 CDNA FLJ31695 fis. clone 1 . . . 424259/425 (60%) e−151 NT2RI2005811. weakly similar to 47 . . . 466 333/425 (77%) cell division control protein 25 - Homo sapiens (Human).473 aa. Q95KH6 Hypothetical 52.9 kDa protein - 1 . . . 424 241/426 (56%)e−132 Macaca fascicularis (Crab eating 47 . . . 459  312/426 (72%)macaque) (Cynomolgus monkey), 466 aa. Q9D300 9130006A14Rik protein - Mus1 . . . 424 235/425 (55%) e−129 musculus (Mouse). 466 aa. 47 . . . 459 309/425 (72%)

[0344] PFam analysis predicts that the NOV4a protein contains thedomains shown in the Table 4F. TABLE 4F Domain Analysis of NOV4aIdentities/ Pfam NOV4a Match Similarities Domain Region for the MatchedRegion Expect Value RasGEF 159 . . . 362 61/236 (26%) 1.5e−11 136/236(58%) 

Example 5

[0345] The NOV5 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 5A. TABLE 5A NOV5 SequenceAnalysis SEQ ID NO:13 1259 bp NOV5a. TGGCCATGGCGTCCCCGGCCATCGGGCAGCGCCCGTACCCGCTACTATTGGACCCCGA CG124599-01 DNASequence GCCGCCGCGCTATCTACAGAGCCTGAGCGGCCCCGAGCTACCGCCGCCGCCCCCCGACCGGTCCTCGCGCCTCTGTGTCCCGGCGCCCCTCTCCACTGCGCCCGGGGCGCGCGAGGGGCGCAGCGCCCGGAGGGCTGCCCGGGGGAACCTGGAGCCCCCGCCCCGGGCCTCCCGACCCGCTCGCCCGCTCCGGCCTGGTCTGCAGCAGAGACTGCGGCGGCGGCCTGGAGCGCCCCGACCCCGCGACGTGCGGAGCATCTTCGAGCAGCCGCAGGATCCCAGAGTCCCGGCGGAGCGAGGCGAGGGGCACTGCTTCGCCGAGTTGGTGCTGCCCGGCGGCCCCGGCTGGTGTGACCTGTGCCGACGAGAGGTGCTGCGGCAGGCGCTGCGCTGCACTGACTGTAAATTCACCTGTCACCCAGAATGCCGCAGCCTGATCCAGTTGGACTGCAGTCAGCAGGAGGGTTTATCCCGGGACAGACCCTCTCCAGAAAGCACCCTCACCGTGAGCTTCAGCCAGAATGTCTGTAAACCTGTGGAGGAGACACAGCGCCCGCCCACACTGCAGGAGATCAAGCAGAAGATCGACAGCTACAACACGCGAGAGAAGAACTGCCTGGGCATGAAACTGAGTGAAGACGGCACCTACACGGGTTTCATCAAAGTGCATCTGAAACTCCGGCGGCCTGTGACGGTGCCTGCTGGGATCCGGCCCCAGTCCATCTATGATGCCATCAAGGAGGTGAACCTGGCGGCTACCACGGACAAGCGGACATCCTTCTACCTGCCCCTAGATGCCATCAAGCAGCTGCACATCAGCAGCACCACCACCGTCAGTGAGGTCATCCAGGGGCTGCTCAAGAAGTTCATGGTTGTGGACAATCCCCAGAAGTTTGCACTTTTTAAGCGCATACACAAGGACGGACAAGTGCTCTTCCAGAAACTCTCCATTGCTGACCGCCCCCTCTACCTGCGCCTGCTTGCTGGGCCTGACACGGAGGTCCTCAGCTTTGTCCTAAAGGAGAATGAAACTGGAGAGGTAGAGTGGGATGCCTTCTCCATCCCTGAACTTCAGAACTTCCTAACAATCCTGGAAAAAGAGGAGCAGGACAAAATCCAACAAGTGCAAAAGAAGTATGACAAGTTTAGGCAGAAACTGGAGGAGGCCTTAAGAGAATCCCAGGGCAAACCTGGGTAA CCG ORF Start: ATG at 6 ORF Stop:TAA at 1254 SEQ ID NO:14 416 aa MW at 46888.2kD NOV5a.MASPAIGQRPYPLLLDPEPPRYLQSLSGPELPPPPPDRSSRLCVPAPLSTAPGAREGR CG124599-01Protein SequenceSARRAARGNLEPPPRASRPARPLRPGLQQRLRRRPGAPRPRDVRSIFEQPQDPRVPAERGEGHCFAELVLPGGPGWCDLCGREVLRQALRCTDCKFTCHPECRSLIQLDCSQQEGLSRDRPSPESTLTVTFSQNVCKPVEETQRPPTLQEIKQKIDSYNTREKNCLGMKLSEDGTYTGFIKVHLKLRRPVTVPAGIRPQSIYDAIKEVNLAATTDKRTSFYLPLDAIKQLHISSTTTVSEVIQGLLKKFMVVDNPQKFALFKRIHKDGQVLFQKLSIADRPLYLRLLAGPDTEVLSFVLKENETGEVEWDAFSIPELQNFLTILEKEEQDKIQQVQKKYDKFRQKLEE ALRESQGKPG

[0346] Further analysis of the NOV5a protein yielded the followingproperties shown in Table 5B. TABLE 5B Protein Sequence Properties NOV5aPSort 0.3000 probability located in microbody (peroxisome): analysis:0.3000 probability located in nucleus: 0.1000 probability located inmitochondrial matrix space: 0.1000 probability located in lysosome(lumen) SignalP No Known Signal Sequence Predicted analysis:

[0347] A search of the NOV5a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table5C. TABLE 5C Geneseq Results for NOV5a NOV5a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAY05724 Rasbinding protein PRE 1-Mus   1..416 348/416 (83%) 0.0 musculus. 413 aa.[WO9916784-  1..413 363/416 (86%) A1. 08-APR-1999] AAY94451 Humaninflammation associated 190..416 225/227 (99%) e−126 protein #8-Homosapiens. 263 aa.  39..265 227/227 (99%) WO200029574-A2. 25-MAY- 2000]AAG02604 Human secreted protein. SEQ ID 190..233  42/44 (95%) 1e−17NO:6685-Homo sapiens. 83 aa.  39..82  43/44 (97%) [EP1033401-A2.06-SEP-2000] AAO05504 Human polypeptide SEQ ID NO 288..342  34/55 (61%)2e−11 19396-Homo sapiens. 84 aa.  28..82  42/55 (75%) [WO200164835-A2.07-SEP-2001] AAM41428 Human polypeptide SEQ ID NO 275..406  43/143 (30%)1e−08 6359-Homo sapiens. 329 aa. 185..324  76/143 (53%) (WO200153312-A1.26-JUL-2001]

[0348] In a BLAST search of public sequence datbases, the NOV5a proteinwas found to have homology to the proteins shown in the BLASTP date inTable 5D. TABLE 5D Public BLASTP Results for NOV5a NOV5a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q8WWW0 Putativetumor suppressor RASSF3 1 . . . 416 415/416 (99%) 0.0 isoform A - Homosapiens (Human). 3 . . . 418 416/416 (99%) 418 aa. Q9BT99 Similar toprotein interacting with 1 . . . 380 378/380 (99%) 0.0 guaninenucleotide exchange factor 1 . . . 380 380/380 (99%) (Hypothetical 43.9kDa protein) - Homo sapiens (Human). 390 aa. O35141 Maxp1 - Rattusnorvegicus (Rat). 1 . . . 416 361/416 (86%) 0.0 413 aa. 1 . . . 413380/416 (90%) O70407 Putative ras effector Nore1 - Mus 1 . . . 416348/416 (83%) 0.0 musculus (Mouse). 413 aa. 1 . . . 413 363/416 (86%)Q8WWV9 Putative tumor suppressor RASSF3 1 . . . 328 327/328 (99%) 0.0isoform B - Homo sapiens (Human). 3 . . . 330 328/328 (99%) 336 aa.

[0349] PFam analysis predicts that the NOV5a protein contains thedomains shown in the Table 5E. TABLE 5E Domain Analysis of NOV5aIdentities/ NOV5a Match Similarities Expect Pfam Domain Region for theMatched Region Value DAG_PE-bind 121 . . . 168 14/51 (27%) 0.00015 32/51(63%) DC1 133 . . . 169  9/48 (19%) 0.54 25/48 (52%) PHD 134 . . . 19710/67 (15%) 0.6 41/67 (61%) RA 270 . . . 362 31/114 (27%)  7.3e−2886/114 (75%) 

Example 6

[0350] The NOV6 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 6A. TABLE 6A NOV6 SequenceAnalysis SEQ ID NO:15 1293 bp NOV6a. CTTGCCTGCCTGCCATGGCCGACAAGGAAGCAGCCTTTGACGACGCAGTGGAAGAACG CG125142-01 DNA SequenceAGTGATCAACGAGGAGTACAAAAATGGAAAAAGAACACCCCTTTTCTTTATGATTTGGTGTTGACCCATGCTCTGGAGTGGCCCAGCCTAACTGCCCAGTGGCTTCCAGATGTAACCAGACCAGAAGGGAAAGATTTCAGCATTCATCAACTTGTCCTGGGGACATGCACATTGGATGAACAAAACCATCTCGTTATAGCCAGTGTGCAACTCCCTAATGATGACACTCAGTTTGATGCGTCACACTACAACACTGAGAAAGGAGAATTTGGAGGTTTTTATTCAGTTAGAGGAAAAATTGAAATAGAAATCAACATCAACCATGAAGGAGAAGTGAACAAGGTCCGTTATATGCCCCAGAACCCTTGTATCATCTCAACTAAGACTCCTTCCAGTCATGTTCTTGTCTTTGACTATACAAAACACCCTTCTAAACCAGATCCTTCTGGAGAGTGCAATCCAGACTTGTGTCTCTGTGGACATCAGAAGGAAGGCTATGGGCTTTCTTGGAACCCAAATCTCTGTGGGCACTTACTTGGTGCTTCAGATGACCACACCAGCTGCCTGTGGGACAGCAGTGCTGTCCCAAAGGAGGGAAAAGTGGTGGATGTGAAGATCATCTTTACAGGGCATACAGCAGTAGTAGAAGATGTTTCCTGGCATCTGCTCCATGAGTCTCTGTTTGGGTCAGTTGCTGATGATCAGAAACTTATGATTTGGGATACTTGTTCAAACAGTGCTTCCAAACCAAGCCATTCAGTTGACGCTCACACTGCTGAAGTGTGCCTCTCTTTCAATCCTTATAGTGAGTTCATTCTTGCCACAGGATCCGCTGACAAGACTGTTGCCTTGCGGGATCTGAGAAATCTGAAACTTAAGTTGCATTCCTTTGAATTACTTAAGGATAAAATATTCCAGGTTCAGTGGTCACCTCACAATGAGACTATTTTGGCTTCCAGTGGTACCAATCACAGACTGAATGTCTGGGATTTAAGTAAAATTGGAGAGAAACAATCCCCAGAAGATAAAAAAGACAGGCCACCAGAGTTATTGTTTATTCATGGTGGTCACACTGCCAAGATACCTGATTTCTCCGGGAATCCCAACGAACCTTGGGTGATTTGTTCTGTACCAGAACACAATATTATGCAAGTGTGGCAAATGGCAGAGAACATTTACAACAATGAAGACCCTGAAGGAAGCGTGGATCCAGAAGG ACAAGAGTCCTAGATAT ORF Start: ATG at 15 ORF Stop: TAG at 1287 SEQ ID NO:16 424 aa MWat 47547.6kD NOV6a.MADKEAAFDDAVEERVINEEYKKWKKNTPFLYDLVLTHALEWPSLTAQWLPDVTRPEG CG125142-01Protein SequenceKDFSIHQLVLGTCTLDEQNHLVIASVQLPNDDTQFDASHYNTEKGEFGGFYSVRGKIEIEININHEGEVNKVRYMPQNPCIISTKTPSSDVLVFDYTKHPSKPDPSGECNPDLCLCGHQKEGYGLSWNPNLCGHLLGASDDHTSCLWDSSAVPKEGKVVDVKIIFTGHTAVVEDVSWHLLHESLFGSVADDQKLMIWDTCSNSASKPSHSVDAHTAEVCLSFNPYSEFILATGSADKTVALRDLRNLKLKLHSFELLKDKIFQVQWSPHNETILASSGTNHRLNVWDLSKIGEKQSPEDKKDRPPELLFIHGGHTAKIPDFSGNPNEPWVICSVPEDNIMQVWQMAENIYNNEDPEGSVDPEGQES

[0351] Further analysis of the NOV6a protein yielded the followingproperties shown in Table 6B. TABLE 6B Protein Sequence Properties NOV6aPSort 0.4500 probability located in cytoplasm: 0.1131 analysis:probability located in microbody (peroxisome). 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probability located inlysosome (lumen) SignalP No Known Signal Sequence Predicted analysis:

[0352] A search of the NOV6a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table6C. TABLE 6C Geneseq Results for NOV6a NOV6a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patene Match theMatched Expect Identifier #, Date] Residues Region Value AAU82965 Humanhomologue of RSA2 protein  1..424 384/425 (90%) 0.0 target forantifungal compound-  1..425 396/425 (92%) Homo sapiens. 425 aa.[WO200202055-A2. 10-JAN-2002] AAG75145 Human colon cancer antigenprotein  1..424 384/425 (90%) 0.0 SEQ ID NO:5909-Homo sapiens. 42..466396/425 (92%) 466 aa. WO200122920-A2. 05- APR-2001] AAB43552 Humancancer associated protein  1..424 384/425 (90%) 0.0 sequence SEQ IDNO:997-Homo 42..466 396/425 (92%) sapiens. 466 aa. [WO200055350- A1.21-SEP-2000] AAR65232 Retinoblastoma binding protein p48  1..424 384/425(90%) 0.0 (RbAp48)-Homo sapiens. 425 aa.  1..425 396/425 (92%)[WO9505392-A. 23-FEB-1995] AAR85892 WD-40 domain-contg. human  1..424384/425 (90%) 0.0 retinoblastoma binding protein-  1..425 396/425 (92%)Homo sapiens. 425 aa. [WO9521252-A2. 10-AUG-1995]

[0353] In a BLAST search of public sequence datbases, the NOV6a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 6D. TABLE 6D Public BLASTP Results for NOV6a NOV6a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q09028 Chromatinassembly factor 1 subunit C 1 . . . 424 384/425 (90%) 0.0 (CAF-1 subunitC) (Chromatin 1 . . . 425 396/425 (92%) assembly factor 1 p48 subunit)(CAF-I 48 kDa subunit) (CAF-1p48) (Retinoblastoma binding protein p48)(Retinoblastoma-binding protein 4) (RBBP-4) (MSI1 protein homolog) -Homo sapiens (Human), 425 aa. Q60972 Chromatin assembly factor 1 subunitC 1 . . . 424 383/425 (90%) 0.0 (CAF-1 subunit C) (Chromatin 1 . . . 425396/425 (93%) assembly factor 1 p48 subunit) (CAF-1 48 kDa subunit)(CAF-Ip48) (Retinoblastoma binding protein p48) (Retinoblastoma-bindingprotein 4) (RBBP-4) - Mus musculus (Mouse). 461 aa. Q9W715 Chromatinassembly factor 1 p48 1 . . . 424 383/425 (90%) 0.0 subunit - Gallusgallus (Chicken), 425 1 . . . 425 395/425 (92%) aa. O93377Retinoblastoma A associated protein - 1 . . . 424 375/425 (88%) 0.0Xenopus laevis (African clawed frog). 1 . . . 425 392/425 (92%) 425 aa.Q24572 Chromatin assembly factor 1 P55 7 . . . 414 340/409 (83%) 0.0subunit (CAF-1 P55 subunit) (DCAF- 11 . . . 419  373/409 (91%) 1)(Nucleosome remodeling factor 55 kDa subunit) (NURF-55) - Drosophilamelanogaster (Fruit fly). 430 aa.

[0354] PFam analysis predicts that the NOV6a protein contains thedomains shown in the Table 6E. TABLE 6E Domain Analysis of NOV6aIdentities/ Pfam NOV6a Match Similarities Domain Region for the MatchedRegion Expect Value WD40 169 . . . 206 12/38 (32%) 0.3 29/38 (76%) WD40219 . . . 256  8/38 (21%) 0.38 28/38 (74%) WD40 265 . . . 301 15/38(39%) 0.16 29/38 (76%) WD40 308 . . . 345  6/38 (16%) 0.096 30/38 (79%)

Example 7

[0355] The NOV7 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 7A. TABLE 7A NOV7 SequenceAnalysis SEQ ID NO: 17 1269 bp NOV 7a.ATGGAAGGAGACTTCTCGGTGTGCAGGAACTGTAAAAGACATGTAGTCTCTGCCAACT CG125414-01DNA Sequence TCACCCTCCATGAGGCTTACTGCCTGCGGTTCCTGGTCCTGTGTCCGGAGTGTGAGGAGCCTGTCCCCAAGGAAACCATGGAGGAGCACTGCAAGCTTGAGCACCAGCAGGCCAATGAGTGCCAGGAGCGCCCTGTTGAGTGTAAGTTCTGCAAACTGGACATGCAGCTCAGCAAGCTGGAGCTCCACGAGTCCTACTGTGGCAGCCGGACAGAGCTCTGCCAAGGCTGTGGCCAGTTCATCATGCACCGCATGCTCGCCCAGCACAGAGATGTCTGTCGCAGTGAACAGGCCCAGCTCGGGAAAGGGGAAAGAATTTCAGCTCCTGAAAGGGAAATCTACTGTCATTATTGCAACCAAATGATTCCAGAAAATAAGTATTTCCACCATATGGGTAAATGTTGTCCAGACTCAGAGTTTAAGAAACACTTTCCTGTTGGAAATCCAGAAATTCTTCCTTCATCTCTTCCAACTCAAGCTGCTGAAAATCAAACTTCCACGATGGAGAAAGATGTTCGTCCAAAGACAAGAAGTATAAACAGATTTCCTCTTCATTCTGAAAGTTCATCAAAGAAAGCACCAAGAAGCAAAAACAAAACCTTGGATCCACTTTTGATGTCAGAGCCCAAGCCCAGGACCAGCTCCCCTAGAGGAGATAAAGCAGCCTATGACATTCTGAGGAGATGTTCTCAGTGTGGCATCCTGCTTCCCCTGCCGATCCTAAATCAACATCAGGAGAAATGCCGGTGGTTAGCTTCATCAAAAAGGAAAACAAGTGAGAAATTTCAGCTAGATTTGGAAAAGGAAAGGTACTACAAATTCAAAAGATTTCACTTTTAA CACTGGCATTCCTGCCTACTTGCTGTGGTCG+E,unsTCTTGTGAAAGGTGATGGGTTTTATTCGTTGGGCTTTAAAAGAAAAGGTTTGGCAGAACTAAAAACAAAACTCACGTATCATCTCAATAGATACAGAAAAGGCTTTTGATAAAATTCAACTTGACTTCATGTTAAAAACCCTCAACAAACCAGGCGTCGAAGGAACATACCTCAAAATAATAAGAGCCATCTATGACAAAACCACAGCCAACATCATACTGAATGAGCAAAAGCTGGAGCATTACTCTTGAGAAGTAGAACAAGGCACTTCAGTCCTATTCAACATAGTACTGGAAGTCTCGCCACAGCAATCAGGCAAGAGAAAGAAGTAAAAGGCACCC ORF Start: ATG at 1ORF Stop: TAA at 895 SEQ ID NO:18 298 aa MW at 34760.6kD NOV7a.MEGDFSVCRNCKRHVVSANFTLHEAYCLRFLVLCPECEEPVPKETMEEHCKLEHQQAN CG125414-01Protein SequenceECQERPVECKFCKLDMQLSKLELHESYCGSRTELCQGCGQFIMHRMLAQHRDVCRSEQAQLGKGERISAPEREIYCHYCNQMIPENKYFHHMCKCCPDSEFKKHFPVGNPEILPSSLPSQAAENQTSTMEKDVRPKTRSINRFPLHSESSSKKAPRSKNKTLDPLLMSEPKPRTSSPRGDKAAYDILRRCSQCGILLPLPILNQHQEKCRWLASSKRKTSEKFQLDLEKERY YKFKRFHF SEQID NO: 19 977 bp NOV 7b. ATCGCCCTTATGGAAGGAGACTTCTCGGTGTGCAGGAACTGTAAAAGACATGTAGTCT CG125414-02 DNASequence CTGCCAACTTCACCCTCCATGAGGCTTACTGCCTGCGGTTCCTGGTCCTGTGTCCGGAGTGTGAGGAGCCCGTCCCCAAGGAAACCATGGAGGAGCACTGCAAGCTTGAGCACCAGCAGGTTGGGTGTACGATGTGTCAGCAGAGCATGCAGAAGTCCTCGCTGGAGTTTCATAAGGCCAATGAGTGCCAGGAGCGCCCTGTTGAGTGTAAGTTCTGCAAACTGGACATGCAGCTCAGCAAGCTGGAGCTCCACGAGTCCTACTGTGGCAGCCGGACAGAGCTCTGCCAAGGCTGTGGCCAGTTCATCATGCACCGCATGCTCGCCCAGCACAGAGATGTCTGTCGCAGTGAACAGGCCCAGCTCGGGAAGGGGGAAAGAATTTCAGCTCCTGAAAGGGAAATCTACTGTCATTATTGCAACCAAATGATTCCAGAAAATAAGTATTTCCACCATATGGGTAAATGTTGTCCAGACTCAGAGTTTAAGAAACACTTTCCTGTTGGAAATCCAGAAATTCTTCCTTCATCTCTTCCAAGTCAAGCTGCTGAAAATCAAACTTCCACGATGGAGAAAGATGTTCGTCCAAAGACAAGAAGTATAAACAGATTTCCTCTTCATTCTGAAAGTTCATCAAAGAAAGCACCAAGAAGCAAAAACAAAACCTTGGATCCACTTTTGATGTCAGAGCCCAAGCCCAGGACCAGCTCCCCTAGAGGAGATAAAGCAGCCTATGACATTCTGAGGAGATGTTCTCAGTGTGGCATCCTGCTTCCCCTGCCGATCCTAAATCAACATCAGGAGAAATGCCGGTGGTTAGCTTCATCAAAAGGAAAACAAGTGAGAAATTTCAGCTAG ATTTGGAAAAGGAAAGGTACTACAAATTCAAAAGATTTCACTTTTAACACTGGCATTCCTGC ORF Start: ATG at 10ORF Stop: TAG at 913 SEQ ID NO: 20 301 aa MW at 34625.4kD NOV7b.MEGDFSVCRNCKRHVVSANFTLHEAYCLRFLVLCPECEEPVPKETMEEHCKLEHQQVG CG125414-02Protein SequenceCTMCQQSMQKSSLEFHKANECQERPVECKFCKLDMQLSKLELHESYCGSRTELCQGCGQFIMHRMLAQHRDVCRSEQAQLGKGERISAPEREIYCHYCNQMIPENKYFHHMGKCCPDSEFKKHFPVGNPEILPSSLPSQAAENQTSTMEKDVRPKTRSINRFPLHSESSSKKAPRSKNKTLDPLLMSEPKPRTSSPRGDKAAYDILRRCSQCCILLPLPILNQHQEKCRWLA SSKGKQVRNFS

[0356] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 7B. TABLE 7B Comparisonof NOV7a against NOV7b. Protein NOV7a Residues/ Identities/ SequenceMatch Residues Similarities for the Matched Region NOV7b 1 . . . 281276/300 (92%) 1 . . . 300 276/300 (92%)

[0357] Further analysis of the NOV7a protein yielded the followingproperties shown in Table 7C. TABLE 7C Protein Sequence Properties NOV7aPSort 0.3600 probability located in mitochondrial matrix analysis:space: 0.3000 probability located in microbody (peroxisome): 0.1000probability located in lysosome (lumen): 0.0000 probability located inendoplasmic reticulum (membrane) SignalP No Known Signal SequencePredicted analysis:

[0358] A search of the NOV7a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table7D. TABLE 7D Geneseq Results for NOV7a NOV7a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAW81072 Aminoacid sequence of the human 1 . . . 298 298/317 (94%)   e−180 XAF-1 withzinc finger motif - 1 . . . 317 298/317 (94%)  Homo sapiens, 317 aa.[EP892048- A2, 20 Jan. 1999] AAY58617 Protein regulating gene expression7 . . . 115 49/127 (38%) 4e−22 PRGE-10 - Homo sapiens, 582 aa. 12 . . .138  68/127 (52%) [WO9964596-A2, 16 Dec. 1999] AAW81077 Amino acidsequences of the human 7 . . . 115 49/127 (38%) 4e−22 XAF-2L - Homosapiens. 582 aa. 12 . . . 138  68/127 (52%) [EP892048-A2. 20 Jan. 1999]AAW81073 Amino acid sequence of the human 7 . . . 115 49/127 (38%) 4e−22XAF-2 with zinc finger motif - 12 . . . 138  68/127 (52%) Homo sapiens,419 aa. [EP892048- A2. 20 Jan. 1999] AAY01364 Human protein with Znfinger-like 7 . . . 115 49/127 (38%) 4e−22 motif - Homo sapiens. 582 aa.12 . . . 138  68/127 (52%) [WO9909158-A1. 25 Feb. 1999]

[0359] In a BLAST search of public sequence datbases, the NOV7a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 7E. TABLE 7E Public BLASTP Results for NOV7a NOV7a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q99982 XIAPassociated factor-1 (ZAP-1) - 1 . . . 298 298/317 (94%)   e−179 Homosapiens (Human). 317 aa. 1 . . . 317 298/317 (94%)  O14545 FLN29 (FLN29gene product) - 7 . . . 115 49/127 (38%) 9e−22 Homo sapiens (Human). 582aa. 12 . . . 138  68/127 (52%) Q8S027 Putative PRL1-interacting factorK - 4 . . . 108 43/154 (27%) 6e−10 Oryza sativa (japonica cultivar- 398. . . 551  65/154 (41%) group), 559 aa. O23395 Similar to UFD1 protein(UFD1 8 . . . 109 41/152 (26%) 2e−08 like protein) - Arabidopsisthaliana 620 . . . 770  61/152 (39%) (Mouse-ear cress), 778 aa. Q8W1E7AT4g15420/d13755w - Arabidopsis 8 . . . 109 41/152 (26%) 2e−08 thaliana(Mouse-ear cress). 561 aa. 403 . . . 553  61/152 (39%)

[0360] PFam analysis predicts that the NOV7a protein contains thedomains shown in the Table 7F. TABLE 7F Domain Analysis of NOV7aIdentities/ Pfam NOV7a Match Similarities Domain Region for the MatchedRegion Expect Value zf-TRAF 23 . . . 80  19/74 (26%) 1.9e−13 52/74 (70%)LIM 93 . . . 143 10/61 (16%) 0.86 31/61 (51%)

Example 8

[0361] The NOV8 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 8A. TABLE 8A NOV8 SequenceAnalysis SEQ ID NO:21 525 bp NOV8a.CGCGTGGCGCCTCTATATTTCCCCGAGAGGTGCGAGGCGGCTGGGCGCACTCGGAGCG CG127770-01DNA Sequence CG ATGGGCGACTGGAAGGTCTACATCAGTGCAGTGCTGCGGGACCAGCGCATCGACGACGTGGCCATCGTGGGCCATGCGGACAACAGCTGCGTGTGGGCTTCGCGGCCCGGGGGCCTGCTGGCGGCCATCTCGCCGCAGGAGGTGGGCGTGCTCACGGGGCCGGACAGGCACACCTTCCTGCAGGCGGGCCTGAGCGTGGGGGGCCGCCGCTGCTGCGTCATCCGCGACCACCTGCTGGCCGAGGGTGACGGCGTGCTGGACGCACGCACCAAGGGGCTGGACGCGCGCGCCGTGTGCGTGGGCCGTGCGCCGCGCGCGCTCCTGGTGCTAATGGGCCGACGCGGCGTACATGGGGGCATCCTCAACAAGACGGTGCACGAACTCATACGCGGGCTGCGCATGCA GGGCGCCTAGCCGGCCAGCCAGGCCGCCCACTGGTAGCGCGGGCCAAATAAACTGTGA CCT ORF Start: ATG at61 ORF Stop: TAG at 472 SEQ ID NO: 22 137 aa MW at 14595.8kD NOV8a.MGDWKVYISAVLRDQRIDDVAIVGHADNSCVWASRPGGLLAAISPQEVGVLTGPDRHT CG127770-01Protein SequenceFLQAGLSVGGRRCCVIRDHLLAEGDGVLDARTKGLDARAVCVGRAPRALLVLMGRRGVHGGILNKTVHELIRGLRMQGA SEQ ID NO: 23 465 bp NOV8b.ATGGGCGACTGGAAGGTCTACATCAGTGCAGTGCTGCGGGACCAGCGCATCGACGACG CG127770-02DNA Sequence TGGCCATCGTGGGCCATGCGGACAACAGCTGCGTGTGGGCTTCGCGGCCCGGGGGCCTGCTGGCGGCCATCTCGCCGCAGGAGGTGGGCGTGCTCACGGGGCCGGACAGGCACACCTTCCTGCAGGCGGGCCTGAGCGTGGGGGGCCGCCGCTGCTGCGTCATCCGCGACCACCTGCTGGCCGAAGGTGACGGCGTGCTGGACGCACGCACCAAGGGGCTGGACGCGCGCGCCGTGTGCGTGGGCCGTGCGCCGCGCGCGCTCCTGGTGCTAATGGGCCGACGCGGCGTACATGGGGGCATCCTCAACAAGACGGTGCACGAACTCATACGCGGGCTGCGCATGCAGG GCGCCTAGCCGGCCAGCCAGGCCGCCCACTGGTAGCGCGGGCCAAATAAACTGTGACC T ORF Start: ATG at IORF Stop: TAG at 412 SEQ ID NO: 24 137 aa MW at 14595.SkD NOV8b.MGDWKVYISAVLRDQRIDDVAIVGHADNSCVWASRPGGLLAAISPQEVGVLTGPDRHT CG127770-02Protein SequenceFLQAGLSVGGRRCCVIRDHLLAEGDGVLDARTKGLDARAVCVGRAPRALLVLMGRRGVHGGILNKTVHELIRGLRMQGA

[0362] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 8B. TABLE 8B Comparisonof NOV8a against NOV8b. Protein NOV8a Residues/ Identities/ SequenceMatch Residues Similarities for the Matched Region NOV8b 1 . . . 137137/137 (100%) 1 . . . 137 137/137 (100%)

[0363] Further analysis of the NOV8a protein yielded the followingproperties shown in Table 8C. TABLE 8C Protein Sequence Properties NOV8aPSort 0.8188 probability located in lysosome (lumen): 0.6500 analysis:probability located in cytoplasm: 0.1000 probability located inmitochondrial matrix space: 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0364] A search of the NOV8a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table8D. TABLE 8D Geneseq Results for NOV8a NOV8a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length ]Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAB19713 Ratprofilin-3-Rattus rattus. 137 aa. 1..135 119/135 (88%) 4e−65[WO200061598-A2. 19-OCT-20001] 1..135 173/135 (90%) ABB57140 Mouseischaemic condition related 1..133  60/136 (44%) 3e−27 protein sequenceSEQ ID NO:335- 1..136  84/136 (61%) Mus musculus. 140 aa.[WO200188188-A2. 22-NOV-2001] AAG6417l 140 aa. [WO200146413-A1. 28-1..139  82/139 (58%) 8e−25 JUN-2001] AAG01415 Human secreted protein.SEQ ID 1..126  54/129 (41%) 2e−23 NO:5496-Homo sapiens, 130 aa. 1..129 77/129 (58%) [EP1033401-A2. 06-SEP-2000] ABG12235 Novel humandiagnostic protein 7..133  48/127 (37%) 2e−19 #12226-Homo sapiens. 122aa. 5..119  79/127 (55%) ]WO200175067-A2. 11-OCT-2001]

[0365] In a BLAST search of public sequence datbases, the NOV8a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 8E. TABLE 8E Public BLASTP Results for NOV8a NOV8a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9DAD61700012P12Rik protein (Profilin- 1 . . . 135 121/135 (89%)  3e−66 III) -Mus musculus (Mouse). 137 1 . . . 135 125/135 (91%)  aa. S04067profilin - mouse. 140 aa. 1 . . . 133 60/136 (44%) 6e−27 1 . . . 13684/136 (61%) P10924 Profilin I - Mus musculus 4 . . . 133 59/133 (44%)2e−26 (Mouse). and. 139 aa. 3 . . . 135 83/133 (62%) A28622 profilin[validated] - human. 140 1 . . . 133 60/136 (44%) 3e−26 aa. 1 . . . 13683/136 (60%) S36804 profilin II - human. 140 aa. 1 . . . 133 59/136(43%) 1e−25 1 . . . 136 83/136 (60%)

[0366] PFam analysis predicts that the NOV8a protein contains thedomains shown in the Table 8F. TABLE 8F Domain Analysis of NOV8aIdentities/ Pfam NOV8a Match Similarities Domain Region for the MatchedRegion Expect Value Profilin 3 . . . 128 29/135 (21%) 3.2e−12 86/135(64%)

Example 9

[0367] The NOV9 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 9A. TABLE 9A NOV9 SequenceAnalysis SEQ ID NO:25 649 bp NOV9a. CCTGGGCATGTGGTATGAGATCAAGGCCCAGGTACACAACATCCACCTGTGCAAAGAC CG127897-01 DNASequence AAACATGGCAAGACTGGGCTGCAGCTGCAGACCACCAACAAGGGGCTCTTTGTGCAGGTCCAGGCCAACACCACTGCATCCCTCATGCTGCTGTGCTTTGGGGACCAAATCCTACAGATTGATGGGCATGACTGTGCCAAGTGGAACATGGAAAAAGCCCATGTTATAAGATGGGAGTCTGGTGACAAGATTGTTATGGTCATTCAGGACAGGATAGTCCAGTGGATTGTCACCATGCACAAGGACAGCACAAGCCATGGTGGCTTCATCATCAAGAAGGGAAAGGTCTTCCCTGTGGTCAAAGGGAGCTCTGGACTCTTCACCAACCACCATGTGTGCCAGGTTCAAGAACGTTTAACAAGCACTGTGCAGAGTGTCATTGGGCTGAAAGAGATCTCAGAGATTCTGGCCACAGCCAGGAACATTGTCACCCTGATCATCATCCCCACTGTGATCTATGAGCACATAGTCAAAAAGTTTTCCCTGACCCATCGCCACCACATATGGACCACTTCATCCCAGATGCCTGAAGCCACAGGAGGGCAGCTTAGGCCCTCCCACCCTCCTGCAGGAAAGGCCA GCCACTCTTGAORF Start: ATG at 8 ORF Stop: TGA at 647 SEQ ID NO: 26 213 aa MW at23880.6kD NOV9a.MWYEIKAQVHNIHLCKDKHGKTGLQLQTTNKGLFVQVQANTTASLMLLCFGDQILQID CG127897-01Protein SequenceGHDCAKWNMEKAHVIRWESGDKIVMVIQDRIVQWIVTMHKDSTSHGGFIIKKGKVFPVVKGSSCLFTNHHVCQVQERLTSTVQSVIGLKEISEILATARNIVTLIIIPTVIYEHIVKKFSLTHRHHIWTTSSQMPEATGGQLRPSHPPAGKASHS

[0368] Further analysis of the NOV9a protein yielded the followingproperties shown in Table 9B. TABLE 9B Protein Sequence Properties NOV9aPSort 0.5336 probability located in microbody (peroxisome): analysis:0.4500 probability located in cytoplasm: 0.2065 probability located inlysosome (lumen): 0.1000 probability located in mitochondrial matrixspace SignalP No Known Signal Sequence Predicted analysis:

[0369] A search of the NOV9a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table9C. TABLE 9C Geneseq Results for NOV9a NOV9a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAY84610 Ahuman membrane associated   4..195 119/200 (59%) 1e−53 organizationalprotein (HJNCT)- 101..292 143/200 (71%) Homo sapiens. 292 aa.[WO20018915-A2. 06-APR-2000] ABB89421 Human polypeptide SEQ ID NO  4..195 118/200 (59%) 3e−53 1797-Homo sapiens. 292 aa. 101..292 143/200(71%) [WO200190304-A2. 29-NOV-2001] AAU17396 Novel signal transductionpathway   4..195 118/200 (59%) 3e−53 protein, Seq ID 961-Homo sapiens.132..323 143/200 (71%) 323 aa. [WO200154733-A1. 02- AUG-2001] AAB42817Human ORFX 0RF2581   4..195 118/200 (59%) 3e−53 polypeptide sequence SEQID  16..207 143/200 (71%) NO:5162-Homo sapiens 207 aa. [WO200058473-A2.05-OCT-2000] AAE13846 Human lung tumour-specific protein   4..178 88/183 (48%) 9e−41 21484-Homo sapiens. 303 aa. 112..288 128/183 (69%)[WO200172295-A2. 04-OCT-2001]

[0370] In a BLAST search of public sequence datbases, the NOV9a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 9D. TABLE 9D Public BLASTP Results for NOV9a NOV9a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9H190 Syntenin 2(Syntenin-2) (Syndecan  4 . . . 195 118/200 (59%) 8e−53 binding protein2) - Homo sapiens 101 . . . 292 143/200 (71%) (Human). 292 aa. Q99JZOSyntenin 2 (Syndecan binding  4 . . . 184 115/189 (60%) 1e−51 protein2) - Mus musculus 101 . . . 283 137/189 (71%) (Mouse). 292 aa. O08992Syntenin 1 (Syndecan binding  4 . . . 178  91/183 (49%) 6e−42 protein I)(Scaffold protein Pbp1) - 108 . . . 284 130/183 (70%) Mus musculus(Mouse). 299 aa. Q9JI92 Syntenin 1 (Syndecan binding  4 . . . 178 90/183 (49%) 2e−41 protein 1) - Rattus norvegicus 109 . . . 285 129/183(70%) (Rat). 300 aa. O88601 Syntenin - Mus musculus (Mouse).  4 . . .178  90/183 (49%) 3e−41 298 aa. 107 . . . 283 129/183 (70%)

[0371] PFam analysis predicts that the NOV9a protein contains thedomains shown in the Table 9E. TABLE 9E Domain Analysis of NOV9aIdentities/ Pfam NOV9a Match Similarities Domain Region for the MatchedRegion Expect Value PDZ 11 . . . 88 57/84 (68%) 0.37

Example 10

[0372] The NOV10 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 10A. TABLE 10A NOV10 SequenceAnalysis SEQ ID NO:27 814 bp NOV10a. CTGCCATCGCTATGTCTCTGCAAAAGACCCCTCCGACCCGAGTGTTCGTGGAACTGGT CG127936-01 DNA SequenceTCCCTGGGCTGACCGGAGCCGGGAGAACAACCTGGCCTCAGGGAGAGAGACGCTACCGGGCTTACGCCACCCCCTCTCCTCAACACAAGCCCAAACTGCTACCCGCGAGGTGCAAGTAAGCGGCACCTCAGAAGTGTCTGCGGGCCCTGACCGGGCGCAGGTGGTGGTGCGAGTGAGCAGCACCAAGGAGGCGGCAGCCGAGGCCAAAAAGAGCGTTTGTCGCCGTCTAGATTACATCACGCAGAGCCTCCAGCAGCAGGGCTTTCAGGCAGAAAATATAACTGTGACAAAGGATTTTAGGAGAGTGGAAAATGCTTATCACATGGAACCAGAGGTATGTATTACATTTACTGAATTTGGAAAAATGCAAAATATTTGTAACTTTCTTGTTGAAAAGCTAGATAGCTCTGTTGTCATCAGCCCACCCCAGTTCTATCATACTCCACGTTCTGTTGAGAATCTTCGGCGGCAAGCCTGTCTTGTTGCTGTTGAGAATGCGTGGCGCAAAGCTCAAGAAGTCTGTAACCTTGTTGGCCAAACCTTAGGAAAACCTTTACTAATCAAAGAAGAAGAAACAAAAGAATGGGAAGGCCAAATAGATGATCACCAGTCATCCAGACTCTCAAGTTCATTAACTGTACAACAAAAAATCAAAAGTGCAACAATACATGCTGCTTCAAAAGTATTTATAACTTTTGAGCTAAAGGGAAAAGAGAAGAGAAAAAAGCACCTTTGA AATTCCAAACAAATTATA TT ORFStart: ATG at 12 ORF Stop: TGA at 792 SEQ ID NO:28 260 aa MW at29153.9kD NOV10a.MSLQKTPPTRVFVELVPWADRSRENNLASGRETLPGLRHPLSSTQAQTATREVQVSGT CG127936-01Protein SequenceSEVSAGPDRAQVVVRVSSTKEAAAEAKKSVCRRLDYTTQSLQQQGFQAENITVTKDFRRVENAYHMEAEVCITFTEFGKMQNICNFLVEKLDSSVVISPPQFYHTPGSVENLRRQACLVAVENAWRKAQEVCNLVGQTLGKPLLIKEEETKEWEGQIDDHQSSRLSSSLTVQQKIKSATIHAASKVFITFEVKGKEKRKKHL SEQ ID NO: 29 807 bp NOV10b.CCTTATGTCTCTGCAAAAGACCCCTCCGACCCGAGTGTTCGTGGAACTGGTTCCCTGG CG127936-02DNA Sequence GCTGACCGGAGCCGGGAGAACAACCTGGCCTCAGGGAGAGAGACGCTACCGGGCTTACGCCACCCCCTCTCCTCAACACAAGCCCAAACTGCTACCCGCGAGGTGCAAGTAAGCGGCACCTCAGAAGTGTCTGCGGGCCCTGACCGGGCGCAGGTGGTGGTGCGAGTGAGCAGCACCAAGGAGGCGGCAGCCGAGGCCAAAAAGAGCGTTTGTCGCCGTCTAGATTACATCACGCAGAGCCTCCAGCAGCAGGGCGTGCAGGCAGAAAATATAACTGTGACAAAGGATTTTAGGAGAGTGGAAAATGCTTATCACATGGAAGCAGAGGTCTGCATTACATTTACTGAATTTGGAAAAATGCAAAATATTTGTAACTTTCTTGTTGAAAAGCTAGATAGCTCTGTTGTCATCAGCCCACCCCAGTTCTATCATACTCCAGGTTCTGTTGAGAATCTTCGACGGCAAGCCTGTCTTGTTGCTGTTGAGAATGCGTGGCGCAAAGCTCAAGAAGTCTGTAACCTTGTTGGCCAAACCTTAGGAAAACCTTTACTAATCAAAGAAGAAGAAACAAAAGAATGGGAAGGCCAAATAGATGATCACCAGTCATCCAGACTCTCAAGTTCATTAACTGTACAACAAAAAATCAAAAGTGCAACAATACATGCTGCTTCAAAAGTATTTATAACTTTTGAGGTAAAGGGAAAAGAGAAGAGAAAAAAGCACCTTTGA AATTCCAAACAAATTATATT ORF Start: ATG at5 ORF Stop: TGA at 785 SEQ ID NO:30 260 aa MW at 29105.SkD NOV10b.MSLQKTPPTRVFVELVPWADRSRENNLASCRETLPGLRHPLSSTQAQTATREVQVSGT 127936-02Protein SequenceSEVSAGPDRAQVVVRVSSTKEAAAEAKKSVCRRLDYITQSLQQQCVQAENITVTKDFRRVENAYHMEAEVCITFTEFGKMQNICNFLVEKLDSSVVISPPQFYHTPGSVENLRRQACLVAVENAWRKAQEVCNLVGQTLGKPLLIKEEETKEWEGQIDDHQSSRLSSSLTVQQKIKSATIHAASKVFITFEVKGKEKRKKHL

[0373] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 10B. TABLE 10BComparison of NOV10a against NOV10b. Protein NOV10a Residues/Identities/ Sequence Match Residues Similarities for the Matched RegionNOV10b 1 . . . 260 250/260 (96%) 1 . . . 260 250/260 (96%)

[0374] Further analysis of the NOV10a protein yielded the followingproperties shown in Table 10C. TABLE 10C Protein Sequence PropertiesNOV10a PSort 0.6000 probability located in nucleus: 0.3000 analysis:probability located in microbody (peroxisome): 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probability located inlysosome (lumen) SignalP No Known Signal Sequence Predicted analysis:

[0375] A search of the NOV10a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table10D. TABLE 10D Geneseq Results for NOV10a NOV10a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAB15923 E.coil proliferation associated  53..251 43/209 (20%) 0.010 proteinsequence SEQ ID NO:280-  30..233 91/209 (42%) Escherichia coli. 246 aa.[WO200044906-A2. 03-AUG-2000] AAG29759 Arabidopsis thaliana protein 66..158 25/94 (26%) 0.051 fragment SEQ ID NO:35462-  41..129 51/94(53%) Arabidopsis thaliana. 350 aa. [EP1033405-A2. 06-SEP-2000] AAG29758Arabidopsis thaliana protein  66..158 25/94 (26%) 0.051 fragment SEQ IDNO:35461-  62..150 51/94 (53%) Arabidopsis thaliana. 371 aa.[EP1033405-A2. 06-SEP-2000] AAB47763 Novel G-protein coupled receptor #3 25..193 41/176 (23%) 3.8 -Homo sapiens. 848 aa. 209..375 73/176 (41%)]WO200181411-A2. 01-NOV-2001] AAB47761 Novel G-protein coupled receptor#1 25..193 41/176 (23%) 3.8 -Homo sapiens. 769 aa. 209..375 73/176 (41%)[WO200181411-A2. 01-NOV-2001]

[0376] In a BLAST search of public sequence datbases, the NOV10a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 10E. TABLE 10E Public BLASTP Results for NOV10a NOV10a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9ESJ7 PLKinteracting protein - Mus 1 . . . 260 215/260 (82%) e−118 musculus(Mouse). 259 aa. 1 . . . 259 228/260 (87%) Q9CX27 4921528N06Rikprotein - Mus 13 . . . 260  206/248 (83%) e−113 musculus (Mouse). 247aa. 1 . . . 247 219/248 (88%) Q9JK12 A1P70 protein - Mus musculus 53 . .. 260  186/208 (89%) e−103 (Mouse). 208 aa (fragment). 1 . . . 208196/208 (93%) Q9CRM0 4921528N06Rik protein - Mus 1 . . . 202 164/202(81%) 6e−88  musculus (Mouse). 255 aa 54 . . . 254  174/202 (85%)(fragment). Q9D615 4921528N06Rik protein - Mus 13 . . . 211  145/199(72%) 4e−73  musculus (Mouse). 176 aa. 1 . . . 176 153/199 (76%)

[0377] PFam analysis predicts that the NOV10a protein contains thedomains shown in the Table 10F. TABLE 10F Domain Analysis of NOV10a PfamNOV10a Match Identities/ Expect Value Domain Region Similarities for theMatched Region

Example 11

[0378] The NOV11 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 11A. TABLE 11A NOV11 SequenceAnalysis SEQ ID NO:31 1335 bp NOV11a.AGTCTCCTCTGGAGAAAATAATCTGTGAAATTATGTGAATAGAGACCATTTTTCAAAA CG127954-01DNA Sequence CA ATGGGGGAAAGAGCAGGAAGTCCAGGTACTGATCAAGAAAGAAAGGCAGGCAAACACCATTATTCTTACTCATCTGATTTTGAAACGCCACAGTCTTCTGGCCGATCATCGCTGGTCAGTTCTTCACCTGCAAGTGTTAGGAGAAAAAATCCTAAAAGACAAACTTCAGATGGCCAAGTACATCACCGGAAACCAAGCCCTAAGGGTCTACCAAACAGAAAGGGAGTCCGAGTGGGATTTCGCTCCCAGAGCCTCAATAGAGAGCCACTTCGGAAAGATACTGATCTTGTTACAAAACGGATTCTGTCTGCAAGACTGCTAAAAATCAATGAGTTGCAGAATGAAGTATCTGAACTCCAGGTCAAGTTAGCTGAGCTGCTAAAAGAAAATAAATCTTTGAAAAGGCTTCAGTACAGACAGGAGAAAGCCCTGAATAAGTTTGAAGATGCCGAAAATGAAATCTCACAACTTATATTTCGTCATAACAATGAGATTACAGCACTCAAAGAACGCTTAAGAAAATCTCAAGAGAAAGAACGGGCAACTGAGAAAAGGGTAAAAGATACAGAAAGTGAACTATTTAGGACAAAATTTTCCTTACAGAAACTGAAAGAGATCTCTGAAGCTAGACACCTACCTGAACGAGATGATTTGGCAAAGAAACTAGTTTCAGCAGAGTTAAAGTTAGATGACACCGAGAGAAGAATTAAGGAGCTATCGAAAAACCTTGAACTGAGTACTAACAGTTTCCAACGACAGTTGCTTGCTGAAAGGAAAAGGGCATATGAGGCTCATGATGAAAATAAAGTTCTTCAAAAGGAGGTACAGCGACTATATCACAAATTAAAGGAAAAGGAGAGAGAACTGGATATAAAAAATATATATTCTAATCGTCTGCCAAAGTCCTCTCCAAATAAAGAGAAAGAACTTGCATTAAGAAAAAATGCATGCCAGAGTGATTTTGCAGACCTGTGTACAAAAGGAGTACAAACCATGGAAGACTTCAAGCCAGAAGAATATCCTTTAACTCCAGAAACAATTATGTGTTACGAAAACAAATGGGAAGAACCAGGACATCTTACTTTGCAATCTCAAAAGCAAGACAGGCATGGAGAAGCAGGGATTCTAAACCCAATTATGGAAAGAGAAGAAAAATTTGTTACAGATGAAGAACTCCATGTCGTAAAACAGGAGGTTGAAAAGCTGGAGGATGGTAAGAAAAAGAGTTTGTTTAAGCATGTGACAAGTCAGCATCCCTTGAGAAAGAAAGAGTG A ORF Start:ATG at 61 ORF Stop: TGA at 1333 SEQ ID NO: 32 424 aa MW at 49547.6kDNOV11a. MGERAGSPGTDQERKAGKHHYSYSSDFETPQSSGRSSLVSSSPASVRRKNPKRQTSDGCG127954-01 Protein SequenceQVHHRKPSRKGLPNRKGVRVGFRSQSLNREPLRKDTDLVTKRILSARLLKINELQNEVSELQVKLAELLKENKSLKRLQYRQEKALNKFEDAENEISQLIFRHNNEITALKERLRKSQEKERATEKRVKDTESELFRTKFSLQKLKEISEARHLPERDDLAKKLVSAELKLDDTERRIKELSKNLELSTNSFQRQLLAERKRAYEAHDENKVLQKEVQRLYHKLKEKERELDIKNIYSNRLPKSSPNKEKELALRKNACQSDFADLCTKGVQTMEDFKPEEYPLTPETIMCYENKWEEPGHLTLQSQKQDRHGEAGILNPIMEREEKFVTDEELHVVKQEVEKLEDGKKKSLFKHVTSQHPLRKKE

[0379] Further analysis of the NOV11a protein yielded the followingproperties shown in Table 11B. TABLE 11B Protein Sequence PropertiesNOV11a PSort 0.9219 probability located in nucleus; 0.3000 probabilityanalysis: located in microbody (peroxisome): 0.1000 probability locatedin mitochondrial matrix space: 0.1000 probability located in lysosome(lumen) SignalP No Known Signal Sequence Predicted analysis:

[0380] A search of the NOV11a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table11C. TABLE 11C Geneseq Results for NOV11a NOV11a Identities/ Residues/Similarities for Geneseq Protein/Organism/Lemgth Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value ABB11820 Humansecreted protein homologue.  95 . . . 400 120/331 (36%) 5e−47 SEQ IDNO:2190—Homo sapiens. 150 . . . 480 188/331 (56%) 683 aa.[WO200157188-A2. 09 AUG 2001] ABB04337 Human uterine globin 40 332 . . .404  73/75 (97%) 3e−36 polypeptide—Homo sapiens, 362 aa.  1 . . . 75 73/75 (97%) [CN1313335-A. 19 SEP 2001] ABB21697 Protein #3696 encodedby probe for  95 . . . 237  61/143 (42%) 3e−28 measuring heart cell gene 29 . . . 171 102/143 (70%) expression—Homo sapiens, 171 aa.[WO200157274-A2, 09 AUG 2001] ABB62559 Drosophila melanogaster  36 . . .284  62/249 (24%) 4e−20 polypeptide SEQ ID NO 14469—  21 . . . 261126/249 (49%) Drosophila melanogaster. 599 aa. [WO200171042-A2. 27 SEP2001] ABB58657 Drosophila melanogaster  36 . . . 424   92/418 (22%)4e−l2 polypeptide SEQ ID NO 2763— 1208 . . . 1612 175/418 (41%)Drosophila melanogaster. 2274 aa. [WO200171042-A2. 27 SEP 2001]

[0381] In a BLAST search of public sequence datbases, the NOV11a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 11D. TABLE 11D Public BLASTP Results for NOV11a NOV11a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q95KB2Hypothetical 50.0 kDa protein - 1 . . . 424 409/430 (95%) 0.0 Macacafascicularis (Crab eating 1 . . . 430 415/430 (96%) macaque) (Cynomolgusmonkey). 430 aa. Q9BWX7 BA342L8.1 (novel protein similar 1 . . . 404403/410 (98%) 0.0 to C21ORF13) - Homo sapiens 1 . . . 410 403/410 (98%)(Human). 697 aa. Q9D5J9 4930431B11Rik protein - Mus 1 . . . 405 307/413(74%) e−168 musculus (Mouse). 419 aa. 1 . . . 412 354/413 (85%) O95447Protein C21orf13 - Homo sapiens 95 . . . 400  120/331 (36%) 1e−46(Human). 670 aa. 137 . . . 467  188/331 (56%) Q9VVD0 CG6652 protein -Drosophila 36 . . . 284   62/249 (24%) 1e−19 melanogaster (Fruit fly).599 aa. 21 . . . 261  126/249 (49%)

[0382] PFam analysis predicts that the NOV11a protein contains thedomains shown in the Table 11E. TABLE 11E Domain Analysis of NOV11a PfamNOV11a Match Identities/ Expect Value Domain Region Similarities for theMatched Region

Example 12

[0383] The NOV12 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 12A. TABLE 12A NOV 12 SequenceAnalysis SEQ ID NO: 33                 2071 bp NOV12a.ACTCTCCTCCCCCGAGCGGCAGCGGCAGCGGCGGCGGCGGCGGCTGCTGCGGGCGCTG CG128132-01DNA Sequence AATGAGAGACGGTGACTGTTCGGGTCGACGAGTGCTACTCTAGGCGGCGGCGGCCGTGGCGGTGAAGCGTGAGGCCGGCATCGTCTTTCCGTCCTCTGAGGCGACGGCCGCGGCTGCACAGGAATAATGTATTTGTGGCCTTGGACATGAGGCAGTCAGTCCTCTGTTGCTGTTCACAGGAATAATGTATTTGTGGCCTTGGACATGAGGCAGTCAGTCCTCTGTTGCTGTTAACATAAGGTCAGGGACTGATGAGGAAAGC ATGGACCTAATGAACGGGCAGGCAAGCAGTGTCAATATTGCAGCTACTGCTTCTGAGAAAAGTAGCAGCTCTGAATCCTTAAGTGACAAAGGCTCTGAATTGAAGAAAAGCTTTGATGCTGTGGTATTCGATGTTCTTAAGGTTACACCAGAAGAATATGCGGGTCAGATAACATTAATGGATGTTCCAGTATTTAAAGCTATTCAACCAGATGAGCTTTCAAGTTGTGGATGGAATAAAAAAGAAAAATATAGTTCTGCACCAAATGCAGTTGCCTTCACAAGAAGATTCAATCATCTAAGCTTTTGGGTTGTTACACAGATTCTTCATGCTCAAACATTAAAAATTAGAGCAGAAGTTTTGAGCCACTATATTAAAACTGCTAAGAAACTGTATGAGCTGAATAACCTTCATCCACTTATGGCAGTGGTTTCTGGCCTACAGAGTCCCCCAATTTTCAGGTTGACTAAAACATGGGCGTTATTAAGTCGAAAACACAAAACTACCTTTGAAAAATTACAATATGTAATGACTPAACAACATAACTACAAAAGACTCAGAGACTATATAAGTAGCTTAAAGATGACACCTTGCATTCCCTATTTAGGTATCTATTTGTCAGATTTAACATACATCGATTCAGCATACCCATCAACTGGCAGCATTCTAGAAAATGAGCAAAGATCAAATTTAATGAATAATATCCTTCGAATAATTTCTGATTTACAGCAGTCTTGTGAATATGATATTCCCATGTTGCCTCATGTCCAAAAATATCTCAACTCTGTTCAGTATATAGAAGAACTACAAAAATTTGTGGAAGACGATAATTACAAGCTTTCATTAAAGATAGAACCAGGGACAAGCACCCCACGTTCTGCTGCTTCCAGAGAAGATTTAGTAGGTCCTGAAGTAGGAGCGTCTCCACAGAGTGGACGAAAAAGTGTGGCAGCTGATAGTAGGTCCTGAAGTAGGAGCGTCTCCACAGAGTGGACGAAAAAGTGTGGCAGCTGAAGGAAGTGCCATAGTTTGCGTTATAATTTCATTCATAAAATGAACACAGCAGPATTTAAGAGTGCAACCTTTCCAAATGCAGGACCAAGACATCTGTTAGATGATAGCGTCATGGAGCCCCATCCGCCATCTCGAGGCCAAGCTGAAAGTTCTACTCTTTCTAGTGGAATATCAATAGGTAGCAGCGATGGTTCTGAACTAAGTGAAGAGACCTCATGGCCTGCTTTTGAAAGGAACACATTATACCATTCTCTCGGCCCCGTCACAAGAGTCGCACGAAATGGCTATCGAAGTCACATGAAGGCCAGCAGTTCTGCAGAATCAGAAGATTTGGCAGTACATTTATATCCAGGAGCTGTTACTATTCAAGGTGTTCTCAGGAGAAAAACTTTGTTAAAAGAAGGCAAAAACCCTACAGTAGCATCTTCGACAAAATATTCCGCAGCTTTGTGTGGGACACAGCTTTTTTACTATGCTGCCAAATCTCTAAAGGCTACCGAAAGAAAACATTTCAAATCAACATCCAATAAGAACGTATCTGTGATAGGATGGATGGTGATGATGGCTGATGACCCTGAACATCCTGATCTCTTCCTGCTGACTGACTCTGAGAAAGGAAATTCGTACAAGTTTCAAGCTGGCAATAGAATGAATGCAATGTTATGGTTTAAGCATTTGAGTGCAGCCTGCCAAAGTACCAAACAACAGGTTCCTACAAACTTGATGACTTTTGAGTAG AAGCCTGAGAAAAAAAGAGAGGTGAACTGTTGCTTCTACGTGACCATGAGGACCTGA ORF Start: ATG at263         ORF Stop: TAG at 2012 SEQ ID NO: 34                 583aa    MW at 65166.4kD NOV 12a.MDLMNGQASSVNIAATASEKSSSSESLSKDGSELKKSFDAVVFDVLKVTPEEYAGQIT CG12288132-01Protein SequenceLMDVPVFKAIQRDELSSCCWNKKEKYSSAPNAVAFTRRPNHVSFWVVREILHAQTLKIRAEVLSHYTKTAKKLYELNNLHALMAVVSGLQSAPIPRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKMTPCIPYLGIYLSDLTYIDSAYPSTGSILENEQRSNLMNNILRIISDLQQSCEYDIPMLPHVQKYLNSVQYIEELQKFVEDDNYKLSLKIEPGTSTPRSAASREDLVGPEVGASPQSGRKSVAAEGALLPQTPPSPRNLIPHGHRKCHSLGYNFIHKMNTAEFKSATFPNAGPRHLLDDSVMEPHAPSRGQAESSTLSSGISIGSSDGSELSEETSWPAFERNRLYHSLGPVTRVARNGYRSHMKASSSAESEDLAVHLYPGAVTIQGVLRRKTLLKEGKKPTVASWTKYWAALCGTQLFYYAAKSLKATERKHFKSTSNKNVSVIGWMVMMADDPEHPDLFLLTDSEKGNSYKFQAGNRMNAMLWFKHLSAACQSNKQQVPTNLM TFE

[0384] Further analysis of the NOV12a protein yielded the followingproperties shown in Table 12B. TABLE 12B Protein Sequence PropertiesNOV12a PSort 0.6500 probability located in cytoplasm; 0.1000 analysis:probability located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0385] A search of the NOV12a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table12C. TABLE 12C Geneseq Results for NOV12a NOV 12a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value ABB97502 Novelhuman protein SEQ ID NO:  1 . . . 583 557/583 (95%) 0.0 770—Homosapiens, 557 aa.  1 . . . 557 557/583 (95%) [WO200222660-A2. 21 MAR.2002] AAB48789 Human prostate cancer—pre-  1 . . . 583 557/583 (95%) 0.0disposing protein. CA7 CG04 -  1 . . . 557 557/583 (95%) Homo sapiens.557 aa. [WO200069879-A2. 23 NOV. 2000] AAM40386 Human polypeptide SEQ IDNO  1 . . . 355 355/355 (100%) 0.0 3531—Homo sapiens, 361 aa.  1 . . .355 355/355 (100%) [WO200153312-A1. 26 JUL. 2001] AAB92626 Human proteinsequence SEQ ID  1 . . . 279 279/279 (100%) e−158 NO:10923—Homo sapiens.279 aa.  1 . . . 279 279/279 (100%) [EP1074617-A2. 07 FEB. 2001]AAU21693 Novel human neoplastic disease 85 . . . 272 188/188 (100%)e−104 associated polypeptide #126—  1 . . . 188 188/188 (100%) Homosapiens. 201 aa. [WO200155163-A1. 02 AUG. 2001]

[0386] In a BLAST search of public sequence datbases, the NOV12a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 12D. TABLE 12D Public BLASTP Results for NOV12a NOV12a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9ERD6 Ral-Aexchange factor RalGPS2 - Mus 1 . . . 583 570/590 (96%) 0.0 musculus(Mouse), 590 aa. 1 . . . 590 575/590 (96%) Q9D2Y7 9130014M22Rikprotein - Mus musculus 1 . . . 544 531/551 (96%) 0.0 (Mouse), 568 aa. 1. . . 551 536/551 (96%) Q9D2K0 4921528G01 Rik protein - Mus musculus 60. . . 583  513/531 (96%) 0.0 (Mouse), 531 aa. 1 . . . 531 518/531 (96%)O15059 KIAA0351 protein - Homo sapiens 5 . . . 583 361/587 (61%) 0.0(Human), 557 aa. 5 . . . 557 437/587 (73%) Q9NW78 Hypothetical 31.9 kDaprotein - 1 . . . 279  279/279 (100%) e−157 Homo sapiens (Human), 279aa. 1 . . . 279  279/279 (100%)

[0387] PFam analysis predicts that the NOV12a protein contains thedomains shown in the Table 12E. TABLE 12E Domain Analysis of NOV12aIdentities/ Similarities NOV12a for the Pfam Domain Match Region MatchedRegion Expect Value RasGEF  46 . . . 237 67/230 (29%) 3.2e−49 147/230(64%)  PH 458 . . . 569 20/112 (18%) 4.2e−11 78/112 (70%)

Example 13

[0388] The NOV13 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 13A. TABLE 13A NOV 13 SequenceAnalysis SEQ ID NO: 35                 1513 bp NOV13a.ATGGGGAAGGCCCCAGGGTCCCTGTGCCCCCAGCAGGGCTCAGCCTGCCGCTCAAAG CG128219-01DNA Sequence ACCCACCTCCCAGCCAGGCCGTGTCCTTGCTCACGGAGTACGCGGCCAGCCTGGGCATCTTCCTGCTCTTCCGGGAGGACCAGCCACCAGGTGAGGCCGGGCCGGGGTTCCCCTTCTCGGTGAGCGCGGAACTGGATGGGGTGGTCTGCCCTGCGGGCACTGCGAATAGCAAGACGGAGGCCAAACAGCAGGCACCGCTCTCTGCCCTCTGCTACATCCCGAGTCAGCTCGAGAACCCAGGTAATGGAGTCGGCCCCCTTCTACCTCCAGTCTCTCGCCCTGGCGCAGAGAACATCCTGACCCATGAGCAGCGCTCCGCAGCGTTCCTGAGCGCCGGCTTTGACCTCCTGTTGGACGAGCGCTCGCCATACTGCGCCTGTAAGGGGACTGTGGCTGGAGTCATCCTGGAGAGGGAGATCCCGCGTGCCAGGCGCCACGTGAACCACATCTACAACCTGCTGGCTCTGGGCACCGGCAGCAGCTGCTGTGCTGGCTGGCTGGAGTTCTCGGGCCAGCAGCTCCACGACTCCCATGGCCTCGTCATCGCCCCCACGGCCCTCCTCAGGTTCTTGTTCCCCCAGCTCCTGCTGGCCACACAGCGGCGCCCCAACCGCAACGACCAGTCCCTGCTGCCCCCCCAGCCAGGGCCCGGACCCCCATTCACCCTCAAGCCCCGCGTCTTCCTGCACCTCTACATCAGCAACACCCCCAAGGGCCCGGCCCCTCACATCAACTATCCACCCCCCTCCGAAGCTGGCCTCCCGCACACCCCACCCATCCCCCTCCACGCCCATGTGCTCGGGCACCTGAAGCCTGTGTGCTACGTGGCGCCCTCGCTCTGTGACACCCACGTGGGCTGCCTGTCAGCCACTCACAACCTCCCACCCTCCCCCCTCCTCCCCCTCCCTGCTCCCCTGCTGCCCCACCTCGTCTCCCCACTCTACACCACCACCCTCATCCTCGCTGACTCATCCCACCACCCTCCCACTCTGAGCACGCCCATCCACACCCCGCCCTCCCTCGACACTCTCCTCGCGCCATCCCTCCCACCTCCCTACGTCCGGACCGCCCTCCACCTCTTTCCACGCCCCCCCCTGCCCCCTTCCGAACCCACCCCTGACACCTGCCCTCGCCTGACCCTCAACTGGAGCCTCCGGCACCCTGGCATCGAGGTTCTGCATCTCCCCACCCCCCGTCTGAAGTCCACTCCCGCCCTGGGCCCTCCCTCCCGTCTCTGCAAGCCCTCCTTTCTCCCGGCCTTTCACCACGCCCCCAGCCCTCTCCCCAACCCCTACCTCCTCGCCTTGAACACCTACGAGGCTGCCAACCCTGGCCCCTACCACCAGCCTCCCAGGCAGCTCTCTCTCCTCCTGCACCACCACCGCCTCCGCCCTTGGCCCTCCAAGCCACTCGTCCGCAAATTCACAAACTGA ACCCACCCTCCGCGCGA CCCAC ORFStart: ATG at 1           ORF Stop: TGA at 1489 SEQ ID NO:36                 496 aa    MW at 52442.1kD NOV13a.MGKAPRVPVPPAGLSLPLKDPPASQAVSLLTEYAASLGIFLLFREDQPPGEAGPGFPF CG128219-01Protein SequenceSVSAELDGVVCPAGTANSKTEAKQQAALSALCYIRSQLENPGNGVGPLLPAVSRPGAENILTHEQRCAALVSAGFDLLLDERSPYWACKGTVAGVILEREIPRARGHVKEIYKLVALGTGSSCCAGWLEFSGQQLHDCHGLVIARRALLRFLRFQLLLATQGGPKGKEQSVLAPQPGPGPPGTLKPRVGLHLYISNTPKGAARDIKYAGPSEGGLPHSPPMRLQAHVLGQLKPVCYVAPSLCDTHVGCLSASDKLARWAVLGLGGALLAHLVSPLYSTSLILADSCHDPPTLSRAIHTRPCLDSVLGPCLPPPYVRTALHLFAGPPVAPSEPTPDTCRGLSLNWSLGDPGOEVVDVATGRVKSSAALGPPSRLCKASFLRAFHQAARAVGKPYLLALKTYEAAKAGPYQEARRQLSLLLDQQGLGAWPSKPLVGKFRN

[0389] Further analysis of the NOV13a protein yielded the followingproperties shown in Table 13B. TABLE 13B Protein Sequence PropertiesNOV13a PSort 0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis: located in microbody (peroxisome); 0.2469 probability locatedin lysosome (lumen); 0.1000 probability located in mitochondrial matrixspace SignalP No Known Signal Sequence Predicted analysis:

[0390] A search of the NOV13a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table13C. TABLE 13C Geneseq Results for NOV13a NOV13a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAU01962 Humansecreted protein 206 . . . 358 134/153 (87%) 2e−71 immunogenic epitopeencoded by  9 . . . 161 136/153 (88%) gene #37—Homo sapiens. 177 aa.[WO200123598-A1. 05 APR. 2001] ABB89869 Human polypeptide SEQ ID NO 205. . . 358 134/154 (87%) 2e−71 2245—Homo sapiens. 176 aa.  8 . . . 161136/154 (88%) [WO200190304-A2, 29 NOV. 2001] AAU02011 Human secretedprotein encoded by 423 . . . 494  72/72 (100%) 8e−35 gene #37—Homosapiens. 72 aa.  1 . . . 72   72/72 (100%) [WO200123598-A1, 05 APR.2001] ABB69810 Drosophila melanogasrer  72 . . . 490 128/460 (27%) 2e−25polypeptide SEQ ID NO 36222— 185 . . . 623 201/460 (42%) Drosophilamelanogaster. 632 aa. [WO200171042-A2. 27 SEP. 2001] AAW54962 Humandouble-stranded adenosine  30 . . . 489 136/505 (26%) 6e−23deaminase—Homo sapiens. 1226 aa.  731 . . . 1213 205/505 (39%)[US5763174-A. 09 JUN. 1998]

[0391] In a BLAST search of public sequence datbases, the NOV13a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 13D. TABLE 13D Public BLASTP Results for NOV13a NOV13a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value AAM22869Hypothetical 61.8 kDa protein -  1 . . . 496 470/496 (94%) 0.0 Homosapiens (Human), 583 aa.  91 . . . 583 475/496 (95%) Q95JT2 Hypothetical59.4 kDa protein -  1 . . . 496 456/496 (91%) 0.0 Macaca fascicularis(Crab eating  70 . . . 562 464/496 (92%) macaque) (Cynomolgus monkey),562 aa. Q95JV3 Hypothetical 61.2 kDa protein -  1 . . . 496 456/496(91%) 0.0 Macaca fascicularis (Crab eating  88 . . . 580 464/496 (92%)macaque) (Cynomolgus monkey), 580 aa. Q9D5P4 4930403J07Rik protein - Mus 19 . . . 496 354/478 (74%) 0.0 musculus (Mouse), 478 aa.  4 . . . 478394/478 (82%) Q62309 Testis nuclear RNA binding  27 . . . 494 163/495(32%) 7e−52 protein - Mus musculus (Mouse), 140 . . . 617 245/495 (48%)619 aa.

[0392] PFam analysis predicts that the NOV13a protein contains thedomains shown in the Table 13E. TABLE 13E Domain Analysis of NOV13aIdentities/ Similarities NOV13a for the Expect Pfam Domain Match RegionMatched Region Value Dsrm 26 . . . 92 19/74 (26%) 0.013 42/74 (57%)A_deamin 174 . . . 261 38/91 (42%) 4.4e−19 56/91 (62%) A_deamin 308 . .. 491 73/198 (37%)  1.6e−31 113/198 (57%) 

Example 14

[0393] The NOV14 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 14A. TABLE 14A NOV14 SequenceAnalysis SEQ ID NO: 37                 1754 bp NOV14a,TTAAAAATCATCTTTGATTATTCTTCTTTTCTAGTAAAATAATATTTAGAAAAAATA A CG128389-01DNA Sequence TGTCAGAGCACAGCAGAAATTCAGATCAACAAGAACTTCTCGATGAGCAGATTAATGAAGATGAAATCTTGGCCAACTTGTCTGCTGAAGAACTGAAAGAACTGCAGTCGGAAATGCAAGTCATGGCCCCTGACCCCAGCCTTCCCGTGGGAATGATTCAGAAAGATCAAACTGACAACCCACCGACAGGAAACTTCAATCATAAATCTCTTCTTGATTATATGTATTGGGAAAAGGCATCCACGCGCATGCTGCAAGAGGAACGAGTTCCTGTCACCTTTGTGAAATCCGAGGAAAACACTCAACAACAGCATGAAGAAATAGAAAAACGTAATAAAAATATGGCCCAGTATTTAAAAGAAAAGCTCAATAATGAAATAGTTGCAAATAAAAGAGAATCPAACGGCAGCAGCAATATCCAAGAAACAGATGAAGAAGATGAAGAAGAAGAAGATGATGATGATGACCACGAAGCAGAACATGATGGTGAAGAGAQTGAACAAACGAACACAGAAGAGGAAGGCAAAGCAAAGGAACAAATTAGAAATTGTGAGAACAACTGCCAGCACGTAACTGACAAAGCATTCAAAGAACAGAGAGACAGACCAGAGGCCCAAGAACAAAGTGAGAAAAAAATATCGAAATTAGATCCTAAGAAGTTAGCTCTAGACACCAGCTTTTTGAAGGTAAGTACAAGGCCTTCAGGAAACCAGACAGACCTGGATGGGAGCTTGAGGAGAGTTAGGAAAAATGATCCTGACATGAAGGAACTCAACCTGAACAACATTGAAAACATCCCCAAAGAAATGTTACTGGACTTTGTCAATGCAATGAAGAAAAACAAGCACATCAAAACATTCAGTTTAGCCAATCTCGGTGCACATGAGAATGTACCATTTCCCTTCGCTAACATCTTCCCTGAAAATAGAAGCATCACCACTCTCAACATCGAGTCCAATTTCATCACAGGTAAAGGGATTCTGGCCATCATGAGGTGTCTCCAGTTTAATGAGACGCTAACTGAGCTTCGGTTTCACAATCAGAGGCACATGTTGGGTCACCATGCTGAAATGGAAATAGCCAGGCTTTTGAAGGCAAACAACACTCTCCTCAAGATGGCCTACCATTTTGAGCTTCCGCGTCCCAGAATCGTGGTCACTAATCTGCTCACCAGGAATCAGGATAAACAAAGGCAGAAACGACAGGAAGAGCAAAAACAGCAGCAACTCAAGGAACAGAAGAAGCTGATAGCCATGTTAGACAATGGGTTGCGGCTGCCCCCTGGGATGTGGGAGCTGTTGGGAGGACCCAAGCCAGATTCCAGAATGCAGGAATTCTTCCAGCCACCGCCACCTCGGCCTCCCAACCCCCAAAATGTCCCCTTTAGTCAACGCAGTGAAATGATGAAAAAGCCATCGCAGGCCCCGAAGTACAGGACAGACCCTGACTCCTTCCCGGTCGTCAAGCTGAAGAGAATCCACCGCAAATCTCGGATGCCGGAAGCCAGAGAACCACCCGAGAAAACCAACCTCAAAGATGTCATCAAAACGCTCAAGCCAGTGCCGAGAAACAGGCCACCCCCATTGGTGGAAATCACTCCCAGAGATCAGCTGCTAAACGACATTCGTCACAGCAGTGTCGCCTATCTTAAACCTGTAAGTACAACCACCGAGAAATCGTGACTCAGCACCCTCCA ORF Start: ATG at 58          ORF Stop: TGA at 1738 SEQID NO: 38                 560 aa    MW at 65132.9kD NOV14a.MSEHSRNSDQEELLDEEINEDEILANLSAEELKELQSAMEVMAPDPSLPVGMIQKDQT CC128389-01Protein SequenceDKPPTGNFNHKSLVDYMYWEKASRRMLEEERVPVTFVKSEEKTQEEHEEIEKRNKNMAQYLKEKLNNEIVANKRESKGSSNIQETDEEDEEEEDDDDDDEGEDDGEESEETNREEEGKAKEQIRNCENNCQQVTDKAFKEQRDRPEAQEQSEKKISKLDPKKLALDTSFLKVSTRPSGNQTDLDGSLRRVRKNDPDMKELNLNNIENIPKEMLLDFVNAMKKNKHIKTFSLANVGADENVAFALANMLRENRSITTLNIESNFITGKGIVAIMRCLQFNETLTELRFHNQRHMLGHHAEMEIARLLKANNTLLKMGYHFELPGPRMVVTNLLTRNQDKQRQKRQEEQKQQQLKEQKKLIAMLENGLGLPPGMWELLGGPKPDSRMQEFFQPPPPRPPNPQNVPFSQRSEMMKKPSQAPKYRTDRDSFRVVKLKRIQRKSRMPEAREPPEKTNLKDVIKTLKRVPRNRPPPLVEITPRDQLLNDIRHSSVAULKPVSRRREKW

[0394] Further analysis of the NOV14a protein yielded the followingproperties shown in Table 14B. TABLE 14B Protein Sequence PropertiesNOV14a Psort 0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis: located in space; 0.1000 probability located in lysosome(lumen) SignalP No Known Signal Sequence Predicted analysis:

[0395] A search of the NOV14a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table14C. TABLE 14C Geneseq Results for NOVl4a NOV 14a Identities/ Residues/Similarities Geneseq Protein/Organism/Length Match for the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAO11834 Humanpolypeptide SEQ ID NO  1 . . . 268 267/268 (99%)  e−152 25726—Homosapiens.  6 . . . 273 267/268 (99%) 273 aa. [WO200164835-A2. 07 SEP.2001] AAM25794 Human protein sequence 321 . . . 494 173/174 (99%) 3e−99SEQ ID NO: 1309—Homo sapiens.  1 . . . 174 174/174 (99%) 174 aa.[WO200153455-A2. 26 JUL. 2001] AAB86278 Human DCMAG-1 protein—Homo  16 .. . 553 217/571 (38%) 4e−90 sapiens. 552 aa.  14 . . . 540 308/571 (53%)[WO200146388-A2. 28 JUN. 2001] AAW90172 Human heart muscle specific  16. . . 553 2l7/57I (38%) 4e−90 protein—Homo sapiens.  14 . . . 540308/571 (53%) 552 aa. [WO9856907-A1. 17 DEC. 1998] AAU19573 Humandiagnostic and therapeutic 8 . . . 409 175/402 (43%) 2e−85 polypeptide(DITHP) #159—Homo 35 . . . 396 249/402 (61%) sapiens. 531 aa.[WO200162927- A2. 30 AUG. 2001]

[0396] In a BLAST search of public sequence datbases, the NOV14a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 14D. TABLE 14D Public BLASTP Results for NOV14a NOV14a Identities/Protein Residues/ Similarities Accession Match for the Expect NumberProtein/Organism/Length Residues Matched Portion Value Q96LS4 CDNAFLJ25123 fis, clone  75 . . . 443 346/369 (93%) 0.0 CBR06154 - Homosapiens (Human),  1 . . . 347 347/369 (93%) 348 aa. S18732 autoantigen,64 K - human, 572 aa.  32 . . . 553 204/610 (33%) 2e−68  1 . . . 565301/610 (48%) P29536 Leiomodin 1 (Leiomodin, muscle  32 . . . 553204/610 (33%) 2e−68 form) (64 kDa autoantigen D1) (64  1 . . . 565301/610 (48%) kDa autoantigen 1D) (64 kDa autoantigen 1D3)(Thyroid-associated ophthalmopathy autoantigen) (Smooth muscleleiomodin) (SM-Lmod) - Homo sapiens (Human), 572 aa. Q99PM7 Cardiacleiomodin - Mus musculus 257 . . . 553 132/331 (39%) 1e−55 (Mouse), 333aa (fragment).  5 . . . 326 181/331 (53%) Q9NZR1 Tropomodulin 2 - Homosapiens  16 . . . 407 135/393 (34%) 4e−50 (Human), 351 aa.  13 . . . 351206/393 (52%)

[0397] PFam analysis predicts that the NOV14a protein contains thedomains shown in the Table 14E. TABLE 14E Domain Analysis of NOV14aIdentities/ Similarities NOV14a for the Expect Pfam Domain Match RegionMatched Region Value WH2 534 . . . 553 8/21 (38%) 0.83 17/21 (81%) 

Example 15

[0398] The NOV15 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 15A. TABLE 15A NOV 15A SequenceAnalysis SEQ ID NO: 39                 2768 bp NOV15a.GCATTGCATGTTTGTTTGCCATTGCCCCCGCCACCCTGCAAGTTGCACCTTCTAGAPA CG128613-01DNA Sequence CAGCAAGCCAAGCTCCTCTCACCCAGCGTAATGATGCGGAAATGCAAATGCACCATCATGTTGTGACCCATATTGCGAAAATTAGAAAAAAGGAAGTTGTGTTTCGCTATTGCACGAAGTTCAGCCCAGAGGAGAAACTCGCTCGCCTTCAGAAGACAGTACCTCCTAAATGGCTCTACTTTGAACCTGCTGGGCAAGGAAGAGATTTTCAAGGAAACCATCTACCGTGTGCAAGCTCCTGCCGGCCAACCCCAGACCCCAGCACCGAGCCACCCGCCTGTGCCCGCCAAAAGCTCCTGCCGGCCAACCCCAGACCCCAGCACGGAGCCAGGCGCCTGTGCCCGCCAACCTCACCCCAGTCAGCTCACCTTTAAGG ATGGAGTCACCCAGGGGGTCCTCAACCCCTCCAGGACCCATTGCTGCCCTAGGGATGCCAGACACTGGGCCTGGCAGTTCCTCCCTAGGGAAGCTTCAGGCGCTCCCTCTTGGGCCCAGAGCCCACTCTGGGCACCCTCTCACCCTGCCTCCAGCAGCCCACGGCTCTCCAGACATACCCCCCACGGGAGAGCTGAGTGGTACCTTAAAGATCCCCAACCCGCACAGCCGGATCGACAGTCCCTCCTCCACTGTGGCTGCACAGAACTTTCCCTCCGACGAGGCCTTCCAGGCTGGCCCAAGCCCCACTGTACTGCGCGCCCACGCAGAGATCGCCCTCGACAGCCAGGTCCCGAAGGTCACCCCCCAGGAGGACGCGCACAGCGACCTGGCTGAGCAACCTCACTCTGAGAACACCCCCCAGAACGCTGACAACGATCCCCCCCTGGCCCAGCACTCTGGCCCCCAGAAGCTTCTCCACATTGCCCAGCAGCTCCTCCACACCCACCAGACCTATCTCAACCGCCTGCACCTGCTCCACCAGCTTTTCTGCACCACCCTGACGGATCCGCGGATCCCTCCAGAAGTCATCATCCCCATATTCTCTAACATCTCCTCCATCCACCCCTTCCACCGCCACTTCCTGCTCCCGGACCTGAAGACGCGGATCACGCAGGAGTCGCACACAAACCCACGCCTCGGCGACATCCTCCACAACCTGGCCCCATTCCTCAAGATCTACGCCGAGTATCTCAACAACTTTGACCGAGCCCTAGCGCTGCTGACCACGTGGACCCACCGCTCCCCACTGTTTAAACACCTCCTCCACACCATCCAGAACCAGGACGTATGCCGGAACCTGACGCTGCACCACCACATGCTCCAGCCCGTGCAGACGGTCCCCCGGTACGAGCTGCTGCTCAACCACTATCTGAAGAGCCTCCCGCACGACGCCCCACACCGGAAGGATGCGGAGAGGTCCTTGGAGCTCATCTCCACAGCCGCCAACCACTCCAATGCTGCCATTCGGAAAGTGGAGAAAATGCACAAGCTCTTGGAGGTGTACGAGCAGCTGGGTGGGGAAGAAGACATTGTCAACCCCGCCAATGAACTGATCAAGGAGGGCCAAATCCAGAAACTGTCAGCCAAGAACGGCACCCCCCAGGACCGCCACCTCTTCCTGTTCAACAGCATCATCCTTTACTCTCTCCCCAACCTGCGCCTCATCCCCCACAACTTCACCGTCCCCGAGAAGATGGACATCTCAGGCCTCCAGGTGCAGGATATCGTCAAGCCAAACACAGCACATACATTCATCATAACAGCAAGAAAAAGGTCCCTGCAGCTGCAGACCCGGACAGACCAAGAGAAGAAAGAATGCATTCAGATCATCCAGGCCACCATCGAGAAGCACAAACAGAACACCGAAACCTTCAAGGCTTTTGGTGGCGCCTTCAGCCAGCATGAGGACCCCAGCCTCTCTCCAGACATGCCTATCACGAGCACCAGCCCTGTCGAGCCTGTGGTGACCACCGAAGGCAGTTCGGGTGCAGCAGCGCTCGACCCCAGAAAACTATCCTCTAACACCAGACGTGACAAGGACAACCAGAGCTGTAAGAGCTGTGGTGAGACCTTCAACTCCATCACCAAGAGGAGGCATCACTGCAAGCTGTGTGGGGCGGTCATCTGTGGGAAGTGCTCCGAGTTCAAGGCCGAGAACAGCCGGCAGAGCCGTGTCTGCAGAGATTGTTTCCTCACACAGCCAGTGGCCCCTGAGAGCACAGAGGTGGGTGCTCCCAGCTCCTGCTCCCCTCCTGGTGGCGCGGCAGAGCCTCCAGACACCTGCTCCTGTGCCCCAGCAGCTCCAGCTGCCTCTGCTTTCGGAAAGACACCCACTGCACACCCCCAGCCCAGCCTGCTCTGCGCCCCCCTGCGGCTGTCAGAGAGCGGTGAGACCTGGAGCGAGGTGTGGGCCGCCATCCCCATGTCAGATCCCCAGGTGCTGCACCTGCAGGGAGGCAGCCAGGACGGCCGGCTGCCCCGCACCATCCCTCTCCCCAGCTGCAAACTGAGTGTGCCGGACCCTGAGGAGAGGCTGGACTCGGGGCATGTGTGGAAGCTGCAGTGGGCCAAGCAGTCCTGGTACCTGAGCGCCTCCTCCGCAGAGCTGCAGCAGCAGTGGCTGGAAACCCTAAGCACTGCTGCCCATGGGGACACGGCCCAGGACAGCCCGGGGGCCCTCCAGCTTCAGGTCCCTATGGGCGCAGCTGCTCCGTGAGCTGA GTCTCCCACTGCCCTGCACACCACCACATTGGACCTGTGCTGTCCTGGGAGG ORF Start: ATG at435         ORF Stop: TGA at 27O9 SEQ ID NO: 40                 758aa    MW at 82284.0kD NOV15a.MESGRGSSTPRGPIAALGMPDTGPGSSSLGKLQALPVGPRAHCGDPVSLAAAGDGSPD CG128613-01Protein SequenceIGPTGELSGSLKIPNRDSGIDSPSSSVAGENFPCEEGLEAGPSPTVLGAHAEMALDSQVPKVTPQEEADSDVGEEPDSENTPQKADKDAGLAQHSGPQKLLHIAQELLHTEETYVKRLHLLDQVFCTRLTDAGIPPEVIMGIFSNISSIHRFHGQFLLPELKTRITEEWDTNPRLGDILQKLAPFLKMYGEYVKNFDRAVGLVSTWTQRSPLFKDVVHSIQKQEVCGNLTLQHHMLEPVQRVPRYELLLKDYLKRLPQDAPDRKDAERSLELISTAANHSNAAIRKVEKMHKLLEVYEQLGGEEDIVNPANELIKEGQIQKLSAKNGTPQDRHLFLFNSMILYCVPKLRLMGQKFSVREKMDISGLQVQDIVKPNTAHTFIITGRKRSLELQTRTEEEKKEWIQIIQATIEKHKQNSETFKAFGGAFSQDEDPSLSPDMPITSTSPVEPVVTTEGSSGAAGLEPRKLSSKTRRDKEKQSCKSCGETFNSITKRRHHCKLCGAVICGKCSEFKAENSRQSRVCRDCFLTQPVAPESTEVGAPSSCSPPGGAAEPPDTCSCAPAAPAASAFGKTPTADPQPSLLCGPLRLSESGETWSEVWAAIPMSDPQVLHLQGGSQDGRLPRTIPLPSCKLSVPDPEERLDSGHVWKLQWAKQSWYLSASSAELQQQWLETLSTAAHGDTAQDSPGALQLQVPMG AAAP

[0399] Further analysis of the NOV15 a protein yielded the followingproperties shown in Table 15B. TABLE 15B Protein Sequence PropertiesNOV15a PSort 0.3000 probability located in nucleus; 0.1000 probabilityanalysis: located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0400] A search of the NOV15a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table15C. TABLE 15C Geneseq Results for NOV15a NOV15a Identities/ Residues/Similarities Geneseq Protein/Organism/Length Match for the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAU27818 HumanFull-length polypeptide  1 . . . 758 725/758 (95%) 0.0 sequence#143—Homo  1 . . . 725 725/758 (95%) sapiens. 725 aa. [WO200164834-A2.07 SEP. 2001] AAU17096 Novel signal transduction  1 . . . 565 559/565(98%) 0.0 pathway protein. Seq ID 661—  65 . . . 629 559/565 (98%) Homosapiens. 687 aa. [WO200154733-A1. 02 AUG. 2001] AAU17364 Novel signaltransduction 178 . . . 525 287/351 (81%) e−158 pathway protein. Seq ID929—  11 . . . 351 300/351 (84%) Homo sapiens. 363 aa. [WO200154733-A1.02 AUG. 2001] AAU21631 Novel human neoplastic disease  1 . . . 247232/248 (93%) e−132 associated polypeptide #64—Homo  65 . . . 312233/248 (93%) sapiens. 332 aa. [WO200155163-A1. 02 AUG. 2001] AAU17448Novel signal transduction pathway  1 . . . 247 232/248 (93%) e−132protein. Seq ID 1013—Homo  65 . . . 312 233/248 (93%) sapiens. 332 aa.[WO200154733-A1. 02 AUG. 2001]

[0401] In a BLAST search of public sequence datbases, the NOV15a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 15D. TABLE 15D Public BLASTP Results for NOV15a NOV15a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9NXY1 FLJ00004protein - Homo sapiens  1 . . . 628 626/628 (99%) 0.0 (Human), 698 aa(fragment).  65 . . . 692 627/628 (99%) O88842 Faciogenital dysplasiaprotein 3 -  1 . . . 758 551/759 (72%) 0.0 Mus musculus (Mouse), 733 aa. 1 . . . 733 605/759 (79%) O93504 Faciogenital dysplasia protein -  58 .. . 595 338/554 (61%) 0.0 Brachydanio rerio (Zebrafish) (Zebra  52 . . .587 402/554 (72%) danio), 621 aa. P98174 Putative Rho/Rac guaninenucleotide  11 . . . 744 355/758 (46%) e−180 exchange factor (Rho/RacGEF) 232 . . . 929 460/758 (59%) (Faciogenital dysplasia protein) - Homosapiens (Human), 961 aa. Q921L2 Similar to faciogenital dysplasia  10 .. . 744 356/757 (47%) e−179 homolog - Mus musculus (Mouse), 238 . . .928 458/757 (60%) 960 aa.

[0402] PFam analysis predicts that the NOV15a protein contains thedomains shown in the Table 15E. TABLE 15E Domain Analysis of NOV15aIdentities/ Similarities NOV15a for the Expect Pfam Domain Match RegionMatched Region Value RhoGEF 161 . . . 340 75/207 (36%)  8.1e−64 155/207(75%)  PH 371 . . . 469 31/99 (31%) 2.8e−17 79/99 (80%) DAG_PE-bind 528. . . 574 13/51 (25%) 0.99 25/51 (49%) FYVE 532 . . . 584 23/62 (37%)2.8e−12 46/62 (74%) PH 638 . . . 736 16/99 (16%)   9e−06 71/99 (72%)

Example 16

[0403] The NOV 16 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 16A. TABLE 16A NOV16 SequenceAnalysis SEQ ID NO: 41                 1944 bp NOV16a.CAGCCCGCGACAACTCCCGCCACCTACGGGGCCTCAGAGAAGCCGGACTTCGCAAGCA CC128685-01DNA Sequence CC ATGCAGTGGATAACGGGCGGATCGGGAATGCTCATCACTGGAGATTCCATCCTTAGTGCTGAGGCAGTATGCGATCACGTCACCATGGCCAACCGGGAGTTGGCATTTAAAGCTGGCGACGTCATCAAAGTCTTGGATGCTTCCAACAAGGATTGGTGGTGGGGCCAGATCGACGATGAGGAGGGATGGTTTCCTGCCAGCTTTGTGAGGCTCTGGGTGAACCAGGAGGATGAGGTGGACGAGGCGCCCAGCGATGTGCAGAACGCACACCTGCACCCCAATTCAGACTGCCTCTGTCTCGGGCGGCCACTACAGAACCGGGACCAGATGCGGGCCAATGTCATCAATGACATAATGACCACTGAGCGTCACTACATCAAGCACCTCAAGGATATTTGTGAGGGCTATCTGAAGCACTGCCGGAAGAGAAGGCACATGTTCACTGACGAGCAACTGAAGGTAATCTTTGGGAACATTGAAGATATCTACAGATTTCAGATGGGCTTTGTGAGAGACCTGGAGAAACAGTATAACAATGATCACCCCCACCTCAGCCAGATAGCACCCTGCTTCCTAGAGCACCAAGATGGATTCTGGATATACTCTGAGTATTCTAACAACCACCTGGATGCTTGCATGGAGCTCTCCAAACTGATGAAGGACAGCCGCTACCAGCACTTCTTTGAGGCCTGTCGCCTCTTGCAGCAGATCATTGACATTGCTATCGATCGTTTCCTTTTGACTCCAGTGCAGAAGATCTGCAAGTATCCCTTACAGTTGGCTGACCTCCTAAACTATACTGCCCAAGACCACAGTGACTACAGGTATGTGGCAGCTGCTTTGGCTGTCATOAGAAATGTGACTCAGCACATCAACCAACGCAACCCACGTTTAGAGAATATTGACAAGATTGCTCACTCCCACCCTTCTCTCCTAGACTCGCACCCCGAGGACATCCTAGACACGAGCTCCCAGCTCATCTACACTCGCGAGATCCCCTCCATCTACCAGCCCTACCGCCGCAACCAGCAGCGGCTCTTCTTCCTCTTTCACCACCAGATCCTCCTCTCCAACAAGGACCTAATCCCGACAGACATCCTGTACTACAAAGGCCGCATTGACATGGATAAATATGAGGTAGTTGACATTGAGGATGGCAGAGATGATGACTTCAATGTCAGCATGAAGAATGCCTTTAAGCTTCACAACAAGGAGACTGAGCAGATACATCTCTTCTTTCCCAACAAGCTCCAGCAAAAAATACCCTGCCTCACGGCTTTCAGAGAAGAGAGGAAAATGGTACAGGAAGATGAAAAAATTGGCTTTGAAATTTCTGAAAACCAGAAGAGGCAGGCTGCAATGACTGTGAGAAAAGTCCCTAAGCAAAAAGGTGTCAACTCTGCCCGCTCAGTTCCTCCTTCCTACCCACCACCGCAGGACCCGTTAAACCACCGCCACTACCTGGTCCCCGACGGCATCGCTCACTCGCACGTCTTTCACTTCACCGAACCCAAGCGCAGCCAGTCACCATTCTGGCAAAACTTCAGCAGGTTAACCCCCTTCA AAAAATGATACCTACAGGGAGGCAGATAATTTTAAAATAAAGTAAATAAAATTATAATAGATGGACCTTTTTTCGGAGAAGCACTGTTGAAATTTATACACACACACACACACAGACACACACACACAGAGAGATAAGGAACAAAAGTGTTTTCTGTTGTTTTGGGGAAGTGAAGACCCTTGAGTACACATACACACACACACACACACACACACACACACACACACACACACACACACACACAGAGAGATAAGGAACAAAAGTGTTTTCTGTTGTTTTGGGGAAGTGAAATATGTGGTTGGTAGGAAGAGGTACCAATGACTTCCAAACATGTGATTCCGTCTTAAAAGTTTTCCATTTTTACCCTGTCCCCCTTCC ORF Start: ATC at 61          ORF Stop:TGA at 1630 SEQ ID NO: 42                 593 aa    MW at 61740.5kDNOV16a. MQWIRGGSGMLITGDSIVSAEAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDCC128685-01 Protein SequenceDEEGWFPASPVRLWVNQEDEVEEGPSDVQNCHLDPNSDCLCLCRPLQNRDQMRANVINEIMSTERHYIKHLKDICECYLKQCRKRRDMFSDEQLKVIFGNTEJDTYRVQMGFVRDLEKQYNNDDPHLSEIGPCFLEHQDGFWIYSEYCNNHLDACMELSKLMKDSRYQHFFEACRLLQQMIDIAIDGFLLTPVQKICKYPLQLAELLKYTAQDHSDYRTVAAALAVMRNVTQQINERKRRLENIDKIAQWQASVLDWEGEDILDRSSELIYTGEMAWIYQPYGRNQQRVFFLFDHQMVLCKKDLIRRDILYYKGRIDMDKYEVVDIEDGRDDDFNVSMKNAFKLHNKETEEIHLFFAKKLEEKIRWLRAFREERKMVQEDEKIGFEISENQKRQAAMTVRKVPKQKGVNSARSVPPSYPPPQDPLNHGQYLVPDGIAQSQVFEFTEPKRSQSPFWQNFSRLTPFK K

[0404] Further analysis of the NOV16a protein yielded the followingproperties shown in Table 16B. TABLE 16B Protein Sequence PropertiesNOV16a PSort 0.6000 probability located in nucleus; 0.5159 probabilityanalysis: located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located in lysosome(lumen) SignalP No Known Signal Sequence Predicted analysis:

[0405] A search of the NOV16a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table16C. TABLE 16C Geneseq Results for NOV16a NOV16a Identities/ ResiduesSimilarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAM39338 Humanpolypeptide SEQ ID NO  1 . . . 523 523/523 (100%) 0.0 2483 - Homosapiens. 523 aa.  1 . . . 523 523/523 (100%) [WO200153312-A1. 26 JUL.2001] AAM41124 Human polypeptide SEQ ID NO  10 . . . 523 512/514 (99%)0.0 6055 - Homo sapiens, 647 aa. 134 . . . 647 513/514 (99%)[WO200153312-A1, 26 JUL. 2001] AAB97025 Human colon carcinoma  11 . . .523 304/518 (58%) e−179 suppressor gene-related protein - 119 . . . 619383/518 (73%) Homo sapiens. 619 aa. [JP2001057888-A. 06 MAR. 2001]AAU17071 Novel signal transduction pathway 258 . . . 523 263/266 (98%)e−153 protein. Seq ID 636 - Homo  3 . . . 268 265/266 (98%) sapiens. 268aa. [WO200154733- A1. 02 AUG. 200l] AAM84301 Human immune/haematopoietic258 . . . 523 263/266( 98%) e−153 antigen SEQ ID NO:11894 - Homo  3 . .. 268 265/266 (98%) sapiens. 268 aa. [WO200157182- A2. 09 AUG. 2001]

[0406] In a BLAST search of public sequence datbases, the NOV16a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 16D. TABLE 16D Public BLASTP Results for NOV16a NOV16a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value O43307 KIAA0424protein - Homo sapiens  10 . . . 523 513/514 (99%) 0.0 (Human), 516 aa. 3 . . . 516 514/514 (99%) Q9QX73 Collybistin I - Rattus norvegicus  1 .. . 464 456/464 (98%) 0.0 (Rat), 493 aa.  1 . . . 464 460/464 (98%)Q9ER22 Collybistin II - Rattus norvegicus  63 . . . 463 388/401 (96%)0.0 (Rat), 411 aa.  3 . . . 403 391/401 (96%) Q96N96 CDNA FLJ31208 fis,clone  11 . . . 523 318/520 (61%) 0.0 KIDNE2003373, moderately similar143 . . . 652 395/520 (75%) to Homo sapiens Asef APC- stimulated guaninenucleotide exchange factor - Homo sapiens (Human), 652 aa. Q9HDC6APC-stimulated guanine nucleotide  11 . . . 523 304/518 (58%) e−179exchange factor - Homo sapiens 119 . . . 619 383/518 (73%) (Human), 619aa.

[0407] PFam analysis predicts that the NOV16a protein contains thedomains shown in the Table 16E. TABLE 16E Domain Analysis of NOV16aIdentities/ Similarities NOV16a for the Expect Pfam Domain Match RegionMatched Region Value SH3 18 . . . 72 20/58 (34%) 4.1e−07 38/58 (66%)RhoGEF 114 . . . 293 58/207 (28%)  9.5e−35 125/207 (60%)  PH 326 . . .432 21/107 (20%)  9.1e−11 81/107 (76%)  CSD 434 . . . 459 12/28 (43%)0.33 20/28 (71%)

Example 17

[0408] The NOV17 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 17A. TABLE 17A NOV 17 SequenceAnalysis SEQ ID NO. 43           1359bp NOV 17a.GCGCCCGAACCCGCGGCGGCGGTGGGGACG ATGTGGTTCTTTGCCCGGGACCCGGTC CG128937-01DNA Sequence GGGACTTTCCGTTCGAGCTCATCCCGGAGCCCCCAGAGGGCGGCCTGCCCGGGCCCTGGGCCCTGCACCGCGGCCGCAAGAAGGCCACAGGCAGCCCCGTGTCCATCTTCGTCTATGATGTGAAGCCTGGCGCGGAAGAGCAGACCCAGGTGGCCAAAGCTGCCTTCAAGCGCTTCAAAACTCTACGGCACCCCAACATCCTGGCTTACATCGATGGACTGGAGACAGAAAAATGCCTCCACGTCGTGACAGAGGCTGTGACCCCGTTGGGAATATACCTCAAGGCGAGAGTGGAGGCTGGTGGCCTGAAGGAGCTGGAGATCTCCTGGGGGCTACACCAGATCGTGAAAGCCCTCAGCTTCCTGGTCAACGACTGCAGCCTCATCCACAACAATGTCTGCATGGCCGCCGTGTTCGTGGACCGAGCTGGCGAGTGGAAGCTTGGGGGCCTGGACTACATGTATTCGGCCCAGGGCAACGGTGGGGGACCTCCCCGCAAGGGGATCCCCGAGCTTGAGCAGTATGACCCCCCGGAGTTGGCTGACAGCAGTGGCAGAGTGGTCAGAGAGAAGTGGTCAGCAGACATGTGGCGCTTGGGCTGCCTCATTTGGGAAGTCTTCAATGGGCCCCTACCTCGGGCAGCAGCCCTACGCAACCCTGGGAAGATCCCCAAAACGCTGGTGCCCCATTACTGTGAGCTGGTGGGAGCAAACCCCAAGGTGCGTCCCAACCCAGCCCGCTTCCTGCAGAACTGCCGGGCACCTGGTGGCTTCATGAGCAACCGCTTTGTAGAAACCAACCTCTTCCTGGAGGAGATTCAGATCAAAGAGCCAGCCGAGAAGCAAAAATTCTTCCAGGAGCTGAGCAAGAGCCTGGACGCATTCCCTGAGGATTTCTGTCGGCACAAGGTGCTGCCCCAGCTGCTGACCGCCTTCGAGTTCGGCAATGCTGGGGCCGTTGTCCTCACGCCCCTCTTCAAGGTGGGCAAGTTCCTGAGCGCTGAGGAGTATCAGCAGAAGATCATCCCTGTGGTGGTCAAGATGTTCTCATCCACTGACCGGGCCATGCGCATCCGCCTCCTGCAGCAGATGGAGCAGTTCATCCAGTACCTTGACGAGCCAACAGTCAACACCCAGATCTTCCCCCACGTCGTGCTAGTCAGGTCAGCAACTCCGACCACAAATCCTCCAAATCCCCAGAGTCCGACTGGAGCAGCTGGGAAGCTGAGGGCTCCTGGGAACAGGGCTGGCAGGAGCAAGCTCCCAGGAGCCACCTC CTGACGGTACACGGCTGGCCAGCGA ORF Start: ATG at 31    ORF Stop: TGA at 1336 SEQID NO: 44           435 aa    MW at 48383.5kD NOV 17a.MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQT CG128937-01Protein SequenceQVAKAAGKRFKTLRHPNILAYIDGLETEKCLHVVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPELEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSNRFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSSTDRAMRIRLLQQMIQFIQYLDEPTVNTQIFPHVVLVRSATPTTNPPNPQSPTGAAGKLRAPGNRAGRSKLPGATS

[0409] Further analysis of the NOV17a protein yielded the followingproperties shown in Table 17B. TABLE 17B Protein Sequence PropertiesNOV17a PSort 0.5151 probability located in microbody (peroxisome);analysis: 0.4500 probability located in cytoplasm; 0.2278 probabilitylocated in lysosome (lumen); 0.1000 probability located in mitochondrialmatrix space SignalP No Known Signal Sequence Predicted analysis:

[0410] A search of the NOV17a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table17C. TABLE 17C Geneseq Results for NOV17a NOV17a Identities/ ResiduesSimilarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAB65679 Novelprotein kinase, SEQ ID NO:  1 . . . 394 394/394 (100%) 0.0 207- Homosapiens, 808 aa. 1 . . . 394 394/394 (100%) [WO200073469-A2, 07 DEC.2000] AAE11780 Human kinase (PKIN)-14 protein -  1 . . . 394 394/394(100%) 0.0 Homo sapiens, 791 aa.  1 . . . 394 394/394 (100%)[WO200181555-A2. 01 NOV. 2001] AAB43354 Human ORFX ORF3118  1 . . . 394394/394 (100%) 0.0 polypeptide sequence SEQ ID 13 . . . 406 394/394(100%) NO:6236 - Homo sapiens. 820 aa. [WO200058473-A2, 05 OCT. 2000]AAB74457 Human Traf4 binding protein  1 . . . 394 392/394 (99%) 0.0MKinase - Homo sapiens. 832 aa 24 . . . 417 393/394 (99%)[WO200121799-A1. 29 MAR. 2001] AAM40778 Human polypeptide SEQ ID NO 84 .. . 394 306/338 (90%) e−176 5709 - Homo sapiens. 675 aa.  8 . . . 345308/338 (90%) [WO200153312-A1. 26 JUL. 2001]

[0411] In a BLAST search of public sequence datbases, the NOV17a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 17D. TABLE 17D Public BLASTP Results for NOV17a NOV17a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q96KG8 Kinase-likeprotein splice variant 1 . . . 394 394/394 (100%) 0.0 1 - Homo sapiens(Human), 791 1 . . . 394 394/394 (100%) aa. Q96KG9 Kinase-like protein -Homo 1 . . . 394 394/394 (100%) 0.0 sapiens (Human), 808 aa. 1 . . . 394394/394 (100%) Q96KH1 Kinase-like protein splice variant 1 . . . 394394/394 (100%) 0.0 2 - Homo sapiens (Human), 707 1 . . . 394 394/394(100%) aa. Q9HAW5 Telomerase regulation-associated 1 . . . 394 380/394(96%)  0.0 protein - Homo sapiens (Human), 1 . . . 394 382/394 (96%) 786 aa. Q9EQC5 105-kDa kinase-like protein - 1 . . . 393 372/393 (94%) 0.0 Mus musculus (Mouse), 806 aa. 1 . . . 393 378/393 (95%) 

[0412] PFam analysis predicts that the NOV17a protein contains thedomains shown in the Table 17E. TABLE 17E Domain Analysis of NOV17a PfamDomain NOV17a Identities/ Expect Match Region Similarities Value for theMatched Region

Example 18

[0413] The NOV18 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 18A. TABLE 18A NOV18 SequenceAnalysis SEQ ID NO:45            1117 bp NOV18a. CCTGCCATGGCGGCTTCTGCGGCGGAGACGCGCGTGTTTCTGGAGGTGCGGGGACAGC CG132095-01 DNASequence TGCAGAGCGCGCTTCTGATCCTGGGGGAACCGAAAGAAGGAGGTATGCCCATGAATATTTCCATAATGCCATCTTCACTCCAGATGAAAACCCCTGAAGGCTGCACAGAAATCCAGCTTCCAGCAGAGGTCAGGCTTGTACCTTCCTCTTGCCGTGGGCTACAGTTTGTTGTTGGAGATGGACTGCACCTGCGACTGCAGACGCAAGCAAAAATTTCAATGTTTAATCAAAGCTCGCAAACCCAAGAATGTTGCACGTTTTATTGCCAATCCTGCGGTGAAGTCATAATAAAAGACAGGAAGCTCCTCAGGGTGCTCCCACTGCCGAGTGAGAACTGGGGAGCTCTAGTTGGAGAATGGTGTTGTCATCCTGACCCCTTTGCTAATAAATCACTTCATCCGCAAGAGAATGACTGTTTTATTGGAGACTCTTTCTTCTTGGTGAATTTAAGAACCAGTTTGTGGCAGCAGGAACCAAAGGCAAATACCAAAGTAATTTGTAAGCGTTGCAAGGTAATGTTGGGAGAGACCGTGTCATCAGAAACCACCAAGTTTTATATGACAGAGATAATTATTCAGTCATCTGAGAGGAGTTTTCCTATCATACCAAGGTCTTGGTTTGTCCAGAGCGTGATCGCCCAGTGTCTGGTGCAGCTCTCCTCTGCTAGAAGCACTTTTAGATTCACGATTCAAGGTCAGGATGACAAAGTGTATATCTTGCTATGGCTTTTAAATTCAGACAGTTTGGTGATTGAATCTTTGAGAAATTCCAAATATATCAAAAAATTCCCCTTGTTGGAAAACACATTCAAAGCCGATTCTAGTTCTGCCTGGAGTGCTGTCAAGGTCCTCTACCAGCCATGCATCAAAAGCAGGAATGAAAAGCTTGTCAGCTTGTGGGAAAGTGACATCAGCGTCCACCCGCTAACCCTGCCCTCTGCAACCTGCTTGGAGCTGCTGTTGATATTGTCAAAGAGTAATGCCAATCTGCCTTCATCCCTTCGCCGTGTGAATTCCTTTCAGGTGAGCAATGGCTTCTTTTCTA GGCCGTGATTTCTCA ORF Start: ATG at7      ORF Stop: TGA at 1108 SEQ ID NO:46           367 aa    MW at 41216.3kD NOV18aMAASAAETRVFLEVRGQLQSALLILGEPKEGGMPMNISIMPSSLQMKTPEGCTEIQLP CG132095-01Protein SequenceAEVRLVPSSCRGLQGVVGDGLHLRLQTQAKISMFNQSSQTQECCTFYCQSCGEVIIKDRKLLRVLPLPSENWGALVGEWCCHPDPFANKSLHPQENDCFIGDSFFLVNLRTSLWQQEPKANTKVICKRCKVMLGETVSSETTKFYMTEIIIQSSERSFPIIPRSWFVQSVIAQCLVQLSSARSTFRFTIQGQDDKVYILLWLLNSDSLVIESLRNSKYIKKFPLLENTFKADSSSAWSAVKVLYQPCIKSRNEKLVSLWESDISVHPLTLPSATCLELLLILSKSNANLPSSLRRVNSFQVSNGFFSRP SEQ ID NO: 47           144 BP NOV18b, CCTGCCATGGCGGCTTCTGCGGCGGAGACGCGCGTGTTTCTGGAGGTGCGGGGACAGC CG132095-02 DNASequence TGCAGAGCGCGCTTCTGATCCTGGGAGAACCGAAAGAAGGAGGTATGCCCATGAATATTTCCATAATGCCATCTTCACTCCAGATGAAAACCCCTGAAGGCTGCACAGAAATCCAGCTTCCAGCAGAGGTCAGGCTTGTACCTTCCTCTTGCCGTGGGCTACAGTTTGTTGTTGGAGATGGACTGCACCTGCGACTGCAGACGCAAGCAAAATTAGGCACAAAACTGATTTCAATGTTTAATCAAAGCTCGCAAACCCAAGAATGTTGCACGTTTTATTGCCAATCCTGCGGTGAAGTCATAATAAAAGACAGGAAGCTCCTCAGGGTGCTCCCACTGCCGAGTGAGAACTGGGGAGCTCTAGTTGGAGAATGGTGTTGTCATCCTGACCCCTTTGCTAATAAATCACTTCATCCGCAAGAGAATGACTGTTTTATTGGAGACTCTTTCTTCTTGGTGAATTTAAGAACCAGTTTGTGGCAGCAAAGACCTGAACTATCCCCAGTGGAGATGTGCTGTGTTTCTTCTGACAACCATTGTAAATTGGAACCAAAGGCAAATACCAAAGTAATTTGTAAGCGTTGCAAGGTAATGTTGGGAGAGACCGTGTCATCAGAAACCACCAAGTTTTATATGACAGAGATAATTATTCAGTCATCTGAGAGGAGTTTTCCTATCATACCAAGGTCTTGGTTTGTCCAGAGCGTGATCGCCCAGTGTCTGGTGCAGCTCTCCTCTGCTAGAAGCACTTTTAGATTCACGATTCAAGGTCAGGATGACAAAGTGTATATCTTGCTATGGCTTTTAAATTCAGACAGTTTGGTGATTGAATCTTTGAGAAATTCCAAATATATCAAAAAATTCCCCTTGTTGGAAAACACATTCAAAGCCGATTCTAGTTCTGCCTGGAGTGCTGTCAAGGTCCTCTACCAGCCATGCATCAAAAGCAGGAATGAAAAACTTGTCAGCTTGTGGGAAAGTGACATCAGCGTCCACCCGCTAACCCTGCCCTCTGCAACCTGCTTGGAGCTGCTGTTGATATTGTCAAAGAGTAATGCCAATCTGCCTTCATCCCTTCGCCGTGTGAATTCCTTTCAGGTGAGCAATGGCTTCTTTTCTAGGCCGTGA TTTCTC ORF Start: ATG at 7     ORF Stop: TGAat 1183 SEQ ID NO: 48           392 aa    MW at 43958.5kD NOV18b.MAASAAETRVFLEVRGQLQSALLILGEPKEGGMPMNISIMPSSLQMKTPEGCTEIQLP CG132095-02Protein SequenceAEVRLVPSSCRGLQFVVGDGLHLRLQTQAKLGTKLISMFNQSSQTQECCTFYCQSCGEVIIKDRKLLRVLPLPSENWGALVGEWCCHPDPFANKSLHPQENDCFIGDSFFLVNLRTSLWQQRPELSPVEMCCVSSDNJCKLEPKANTKVICKRCKVMLGETVSSETTKFYMTEIIIQSSERSFPIIPRSWFVQSVIAQCLVQLSSARSTFRFTIQGQDDKVYILLWLLNSDSLVIESLRNSKYIKKFPLLENTFKADSSSAWSAVKVLYQPCIKSRNEKLVSLWESDISVHPLTLPSATCLELLLILSKSNANLPSSLRRVNSFQVSNGFFSRP

[0414] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 18B. TABLE 18BComparison of NOV18a against NOV18b. Identities/ NOV18a Residues/Similarities for Protein Sequence Match Residues the Matched RegionNOV18b 1 . . . 367 367/392 (93%) 1 . . . 392 367/392 (93%)

[0415] Further analysis of the NOV18a protein yielded the followingproperties shown in Table 18C. TABLE 18C Protein Sequence PropertiesNOV18a PSort 0.5044 probability located in mitochondrial matrixanalysis: space; 0.4500 probability located in cytoplasm; 0.2257probability located in mitochondrial inner membrane; 0.2257 probabilitylocated in mitochondrial intermembrane space SignalP No Known SignalSequence Predicted analysis:

[0416] A search of the NOV18a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table18D. TABLE 18D Geneseq Results For NOV18a NOV 18a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length[Patent Match theMatched Expect Identifier #, Date] Residues Region Value ABB6344Drosophila melanogaster  95 . . . 195 31/107 (28%) 1.7 polypeptide SEQID NO 16365 - 123 . . . 224 44/107 (40%) Drosophila melanogaster. 482aa. [WO200171042-A2. 27 SEP. 2001] AAB11934 Human MEKK5 - Homo sapiens.208 . . . 317 26/116 (22%) 4.9 1374 aa. [US6080546-A. 494 . . . 58952/116 (44%) 27 JUN. 2000] AAW27283 Apoptosis inducing protein ASK1 -208 . . . 317 26/116 (22%) 4.9 Homo sapiens. 1375 aa 494 . . . 58952/116 (44%) [WO9740143-A1. 30 OCT. 1997]

[0417] In a BLAST search of public sequence datbases, the NOV18a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 18E. TABLE 18E Public BLASTP Results for NOV18a NOV18a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9D0H02610018103Rik protein - Mus  1 . . . 360 282/365 (77%)  e−162 musculus(Mouse), 368 aa.  1 . . . 364 323/365 (88%) Q9NT42 Hypothetical 20.4 kDaprotein -  45 . . . 197 153/178 (85%) 2e−83 Homo sapiens (Human), 182 aa 1 . . . 178 153/178 (85%) (fragment). P47172 Hypothetical 39.9 kDaprotein in 106 . . . 360  61/263 (23%) 4e−08 HOM6-PMT4 intergenicregion - 111 . . . 342 108/263 (40%) Saccharomyces cerevisiae (Baker'syeast), 347 aa. Q9BL30 Hypothetical 80.0 kDa protein - 106 . . . 359 59/284 (20%) 0.005 Caenorhabditis elegans, 716 aa. 437 . . . 707113/284 (39%) O74751 Hypothetical 37.4 kDa protein - 125 . . . 359 54/243 (22%) 0.031 Schizosaccharomyces pombe 105 . . . 321  97/243(39%) (Fission yeast), 332 aa.

[0418] PFam analysis predicts that the NOV18a protein contains thedomains shown in the Table 18F. TABLE 18F Domain Analysis of NOV18a PfamDomain NOV18a Identities/ Expect Match Region Similarities for Value theMatched Region

Example 19

[0419] The NOV19 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 19A. TABLE 19A NOV19 SequenceAnalysis SEQ ID NO: 49           8848 bp NOV19a.TATAACGGTACCGGCGGCGGCAGCGCCGCTGCTCTTCCCTTCTCCTCAGGAGGGGGGC CG132414-01DNA Sequence CA ATGGCTAGCGAGAAGCCGGGCCCGGGCCCGGGGCTCGAGCCTCAGCCCGTGGGGCTCATTGCCGTCGGGGCCGCTGGCGGAGGCGGCGGGGGCAGCGGTGGTGGCGGCACCGGGGGCAGCGGGATGGGGGAGCTAAGGGGGGCGTCCGGCTCCGGCTCGGTGATGCTCCCCGCGGGGATGATTAACCCTTCGGTGCCGATCCGCAACATCCGGATGAAATTCGCAGTGTTGATTGGACTCATACAGGTCGGAGAGGTCAGCAACAGGGACATCGTGGAGACGGTGCTCAACCTGCTGGTTGGTGGAGAATTTGACTTGGAGATGAACTTTATTATCCAGGATGCTGAGAGTATAACATGTATGACAGAGCTTTTGGAGCACTGTGATGTAACATGTCAAGCAGAAATATGGAGCATGTTTACAGCCATTCTACGAAAAAGTGTTCGGAATTTACAGACTAGCACAGAAGTTGGGCTAATTGAACAAGTATTGCTGAAAATGAGTGCTGTAGATGACATGATAGCAGATCTTCTAGTTGATATGTTGGGGGTTCTTGCCAGCTACAGCATCACTGTCAAGGAGTTGAAGCTTTTGTTCAGCATGCTTCGAGGAGAAAGTGGAATCTGGCCAAGACATGCAGTAAAATTATTATCAGTTCTTAATCAGATGCCACAGAGACACGGTCCTGATACTTTTTTCAATTTCCCTGGTTGTAGCGCTGCGGCAATTGCCTTGCCTCCTATTGCAAAGTGGCCTTATCAGAATGGCTTCACCTTAAACACTTGGTTTCGTATGGATCCATTAAATAATATTAATGTTGATAAGGATAAACCTTATCTTTATTGTTTTCGTACTAGCAAAGGAGTTGGTTACTCTGCTCATTTTGTTGGCAACTGTTTAATAGTCACATCATTGAAGTCCAAAGGAAAAGGTTTTCAGCATTGTGTGAAATATGATTTTCAACCACGCAAGTGGTACATGATCAGCATTGTCCACATTTACAATCGATGGAGGAACAGTGAAATTCGGTGTTATGTTAATGGACAACTGGTATCTTATGGTGATATGGCTTGGCATGTTAACACAAATGATAGCTATGACAAGTGCTTTCTTGGATCATCAGAAACTGCTGATGCAAATAGGGTATTCTGTGGTCAACTTGGTGCCGTGTATGTGTTCAGTGAAGCACTCAACCCAGCACAGATATTTGCAATTCATCAGTTAGGACCTGGATATAAGAGTACCTTCAAGTTTAAATCTGAGAGTGATATTCATTTGGCAGAACATCATAAACAGGTGTTATATGATGGGAAACTTGCAAGTAGCATTGCCTTTACATATAATGCTAAGGCCACTGATGCTCAGCTCTGCCTGGAATCATCACCAAAAGAGAATGCATCAATTTTTGTGCATTCCCCACATGCTCTAATGCTTCAGGATGTGAAAGCGATAGTAACACATTCAATTCATAGTGCAATTCATTCAATTGGAGGGATTCAAGTGCTTTTTCCACTTTTTGCCCAATTGGATAATAGGCAGCTCAATGACAGTCAAGTGGAAACAACTGTTGCTACTCTGTTGGCATTCCTGGTTGAACTACTTAAAAGTTCAGTAGCCATGCAAGAACAGATGCTGGGTGGAAAAGGCTTTTTAGTCATTGGCTACTTACTTGAAAAGTCATCAAGAGTTCATATAACTAGAGCTGTCCTGGAGCAATTTTTATCTTTTGCAAAATACCTTGATGGTTTATCTCATGGAGCACCTTTGCTGAAGCAGCTTTGTGATCACATTTTATTTAACCCAGCCATCTGGATACATACACCTGCAAAGGTTCAGCTTTCCCTATACACATATTTGTCTGCTGAATTTATTGGAACTGCTACCATCTACACCACCATACGCAGAGTAGGAACAGTATTACAGCTAATGCACACCTTAAAATATTACTACTGGGTTATTAATCCTGCTGACAGTAGTGGCATTACACCTAAAGGATTAGATGGTCCCCGGCCATCACAAAAAGAAATTATATCACTGAGGGCATTTATGCTACTTTTTCTGAAACAGCTGATACTAAAGGATCGAGGGGTCAAGGAAGATGAACTTCAGAGTATATTAAATTACCTACTTACGATGCATGAGGATGAAAATATTCATGATGTGCTACAGTTACTGGTGGCTTTAATGTCGGAACACCCAGCCTCAATGATACCAGCATTTGATCAAAGAAATGGAATAAGGGTGATCTACAAATTATTGGCTTCTAAAAGTGAAAGTATTTGGGTTCAAGCTTTGAAGGTTCTGGGATACTTTCTGAAGCATTTAGGTCACAAGAGAAAAGTTGAAATTATGCACACCCATAGTCTTTTCACTCTTCTTGGAGAAAGGCTGATGTTGCATACAAACACTGTGACTGTCACCACATACAACACACGCATTTAGGTCACAAGAGAAAAGTTGAAATTATGCACACCCATAGTCTTTTCACTCTTCTTGGAGAAAGGCTGATGTTGCATACAAACACTGTGACTGTCACCACATACAACACACGCATTTAGGTCACAAGAGAAAAGTTGAAATTATGCACACCCATAGTCTTTTCACTCTTCTTGGAGAAAGGCTGATGTTGCATACAAACACTGTGACTGTCACCACATACAACACACTTTATGAGATCTTGACAGAACAAGTATGTACTCAGGTCGTACACAAACCACATCCAGAGCCAGATTCTACAGTGAAAATTCAGAATCCAATGATTCTTAAAGTGGTGGCAACTTTGTTAAAAAACTCTACACCAAGTGCAGAGCTGATGGAAGTTCGTCGTTTATTTTTATCTGATATGATAAAACTTTTCAGTAACAGCCGTGAAAATAGAAGATGCTTATTGCAGTGTTCAGTGTGGCAGGATTGGATGTTTTCTCTTGGCTATATCAATCCTAAAAATTCTGAGGAACAGAAGATTACCGAAATGGTCTACAATATCTTCCGGATTCTTTTGTATCATGCAATAAAATATGAATGGGGAGGCTGGAGAGTCTGGGTGGATACCCTCTCAATAGCCCATTCCAAGGTCACTTATGAAGCTCATAAGGAATACCTAGCCAAAATGTATGAGGAATATCAAAGACAAGAGGAGGAAAACATTAAAAAGGGAAAGAAAGGGAATGTGAGCACCATCTCTGGTCTTTCATCACAGACAACAGGAGCAAAAGGTGGAATGGAAATTCGAGAGATAGAAGATCTTTCACAAAGCCAGAGCCCAGAAAGTGAGACCGATTACCCTGTCAGCACAGATACTCGAGACTTACTCATGTCAACAAAAGTGTCAGATGATATTCTTGGAAATTCAGATAGACCAGGAAGTGGTGTACATGTGGAAGTACATGATCTTTTAGTAGATATAAAAGCAGAGAAAGTGGAAGCAACAGAAGTAAAGCTCGATGATATGGATTTATCACCGGAGACTTTAGTAGGTGGAGAGAATGGTGCCCTTGTGGAGGTTGAATCTCTGTTGGATAATGTATATAGTGCTGCTGTTGAGAAACTCCAGAACAATGTACATGGAAGTGTTGGTATCATTAAAAAAAATGAAGAAAAGGATAATGGTCCATTGATAACATTAGCAGATGAGAAAGAAGACCTTCCCAATAGTAGTACATCATTTCTCTTTGATAAAATACCCAAACAGGAGGAAAAACTACTTCCTGAACTTTCTAGCAATCACATTATTCCAAATATTCAGGACACACAAGTACATCTTGGTGTTAGTGATGATCTTGGATTGCTTGCTCACATGACCGGTAGCGTAGACTTAACTTGTACATCCAGTATAATAGAAGAAAAAGAATTCAAAATCCATACAACTTCAGATGGAATGAGCAGTATTTCTGAAAGAGACTTAGCGTCATCAACTAAGGGGCTGGAGTATGCTGAAATGACTGCTACAACTCTGGAAACTGAGTCTTCTAGTAGCAAAATTGTACCAAATATTGATGCAGGAAGTATAATTTCAGATACTGAAAGGTCTGACGATGGCAAAGAATCAGGAAAAGAAATCCGAAAAATCCAAACAACTACTACGACACAAGGTCGGTCTATCACCCAACAAGACCGAGATCTCCGAGTTGATTTAGGATTTCGAGGAATGCCAATGACTGAGGAACAGCGACGCCAGTTTAGCCCAGGTCCACGGACTACAATGTTTCGTATTCCTGAGTTTAAATGGTCTCCAATGCACCAGCGGCTTCTCACTGATTTACTATTTGCATTAGAAACTGATGTACATGTTTGGAGGAGCCATTCTACAAAGTCTGTAATGGATTTTGTCAATAGCAATGAAAATATTATTTTTGTACATAACACAATTCACCTCATTTCCCAAATGGTAGACAACATCATCATTGCTTGTGGAGGAATTTTACCTTTGCTCTCTGCTGCTACATCACCAACTGGTTCTAAGACGGAATTGGAAAATATTGAAGTGACACAAGGCATGTCAGCTGAGACAGCAGTAACTTTCCTCAGCCGGCTGATGGCTATGGTTGATGTACTTGTGTTTGCAAGCTCTCTAAATTTTAGTGAGATTGAAGCTGAGAAAAACATGTCTTCTGGAGGTTTAATGCGACAGTGCCTAAGATTAGTTTGTTGTGTTGCTGTGAGAAACTGTTTAGAATGTCGGCAAAGACAGAGAGACAGGGGAAATAAATCTTCCCATGGAAGCAGTAAACCTCAGGAAGTTCCTCAAAGTACTCCATTGGAAAATGTTCCAGGTAACCTTTCTCCTATTAAGGATCCGGATAGACTTCTTCAGGATGTTGATATCAATCGCCTTCGTGCTGTTGTCTTTCGGGATGTGGATGATAGCAAACAAGCACAGTTCTTAGCTCTGGCTGTTGTTTACTTCATTTCGGTTCTGATGGTTTCCAAGTATCGTGACATATTAGAACCCCAGAGAGAGACTACAAGAACTGGAAGCCAACCAGGTAGAAACATCAGGCAAGAAATAAATTCACCAACAAGTACAGAAACACCTGCTGCATTTCCAGACACCATAAAAGAAAAAGAAACACCAACTCCTGGTGAAGATATTCAGGTAGAAAGTTCAATTCCCCATACAGATTCAGGAATTGGAGAGGAGCAAGTGGCTAGCATCCTGAATGGGGCAGAATTAGAAACAAGTACAGGCCCTGATGCCATGAGTGAACTCTTATCCACTTTGTCATCCGAAGTGAAGAAATCACAAGAGAGCTTAACTGAAAATCCTAGTGAAACGTAATACTGAAAAGTCTTGTGGCTGCTCCAGTTGAAATAGCAGAATGTGGCCCTGAACCTATCCCATACCCAGATCCAGCATTGAAGAGAGAAACACAAGCTATTCTTCCTATGCAGTTTCATTCCTTTGACAGCATCACTGCAAAACTTGAAAGAGCGTTAGAAAAAGTTGCTCCTCTTCTTCGTGAAATTTTTGTAGACTTTGCCCCATTCCTATCTCGTACACTTCTTGGCAGTCATGGACAAGAGCTATTGATAGAAGGCCTTGTTTGTATGAAGTCCAGCACATCTGTGGTTGAGCTTGTTATGCTGCTTTGTTCTCAGGAATGGCAAAACTCTATTCAGAAGAATGCAGGACTTGCATTTATTGAGCTCATCAATGAAGGAAGATTACTGTGCCATGCTATGAAGGACCATATAGTCCGTGTTGCAAATGAAGCTGAGTTTATTTTGAACAGACAAAGAGCCGAGGATGTACATAAACATGCAGAGTTTGAGTCACAGTGTGCCCAATATGCTGCTGATAGAAGAGAGGAAGAAAAGATGTGTGACCATCTTATCAGTGCTGCTAAACATCGAGATCATGTAACAGCAAATCAGCTGAAACAGAAGATTCTCAATATTCTCACAAATAAACATGGTGCTTGGGGAGCAGTTTCTCATAGCCAATTGCATGATTTCTGGCGTTTGGATTACTGGGAAGATGATCTTCGTCGAAGGAGACGATTTGTTCGCAATGCATTTGGCTCCACTCATGCTGAAGCATTGCTGAAAGCTGCAATAGAATATGGCACGGAAGAAGATGTAGTAAAGTCAAAGAAAACATTCAGAAGTCAAGCAATAGTGAACCAAAATGCAGAGACAGAACTTATGCTGGAAGGAGACGATGATGCAGTCAGTCTGCTACAGGAGAAAGAAATTGACAACCTTGCAGGCCCAGTGGTTCTCAGCACCCCTGCCCAGCTCATCGCTCCCGTGGTGGTGGCCAAGGGGACTCTCTCCATCACCACGACAGAAATCTACTTCGAGGTAGATGAGGATGATTCTGCCTTCAAGAAGATCGACACGAAAGTTCTTGCATACACTGAGGGACTTCACGGAAAATGGATGTTCAGCGAGATACGAGCTGTATTTTCAAGACGTTACCTTCTACAAAACACTGCTTTGGAAGTATTTATGGCAAACCGAACCTCAGTTATGTTTAATTTCCCTGATCAAGCAACAGTAAAAAAAGTTGTCTATAGCTTGCCTCGGGTTGGAGTAGGGACCAGCTATGGTCTGCCACAAGCCAGGAGGATATCATTGGCCACTCCTCGACAGCTTTATAAATCTTCCAATATGACTCAGCGCTGGCAAAGAAGGGAAATTTCAAACTTCGAATATTTGATGTTCCTTAATACTATTGCAGGACGGACATATAATGATCTGAACCAATATCCAGTGTTTCCGTGGGTGTTAACCAACTATGAATCAGAAGAGTTGGACCTGACTCTTCCAGGAAACTTCAGGGATCTATCAAAGCCAATTGGTGCTTTGAACCCCAAGAGAGCTGTGTTTTATGCAGAGCGTTATGAGACATGGGAAGATGATCAAAGCCCACCCTACCATTATAATACCCATTATTCAACAGCAACATCTACTTTATCCTGGCTTGTTCGAATTGAACCTTTCACAACCTTCTTCCTCAATGCAAATGATGGAAAATTTGATCATCCAGATCGAACCTTCTCATCCGTTGCAAGGTCTTGGAGAACTAGTCAGAGAGATACTTCTGATGTAAAGGAACTAATTCCAGAGTTCTACTACCTACCAGAGATGTTTGTCAACAGTAATGGATATAATCTTGGAGTCAGAGAAGATGAAGTAGTGGTAAATGATGTTGATCTTCCCCCTTGGGCAAAAAAACCTGAAGACTTTGTGCGGATCAACAGGATGGCCCTAGAAAGTGAATTTGTTTCTTGCCAACTTCATCAGTGGATCGACCTTATATTTGGCTATAAGCAGCGAGGACCAGAAGCAGTTCGTGCTCTGAATGTTTTTCACTACTTGACTTATGAAGGCTCTGTGAACCTGGATAGTATCACTGATCCTGTGCTCAGGGAGGCCATGGAGGCACAGATACAGAACTTTGGACAGACGCCATCTCAGTTGCTTATTGAGCCACATCCGCCTCGGAGCTCTGCCATGCACCTGTGTTTCCTTCCACAGAGTCCGCTCATGTTTAAAGATCAGATGCAACAGGATGTGATAATGGTGCTGAAGTTTCCTTCAAATTCTCCAGTAACCCATGTGGCAGCCAACACTCTGCCCCACTTGACCATCCCCGCAGTGGTGACAGTGACTTGCAGCCGACTCTTTGCAGTGAATAGATGGCACAACACAGTAGGCCTCAGAGGAGCTCCAGGATACTCCTTGGATCAAGCCCACCATCTTCCCATTGAAATGGATCCATTAATAGCCAATAATTCAGGTGTAAACAAACGGCAGATCACAGACCTCGTTGACCAGAGTATACAAATCAATGCACATTGTTTTGTGGTAACAGCAGATAATCGCTATATTCTTATCTGTGGATTCTGGGATAAGAGCTTCAGAGTTTATTCTACAGAAACAGGGAAATTGACTCAGATTGTATTTGGCCATTGGGATGTGGTCACTTGCTTGGCCAGGTCCGAGTCATACATTGGTGGGGACTGCTACATCGTGTCCGGATCTCGAGATGCCACCCTGCTGCTCTGGTACTGGAGTGGGCGGCACCATATCATAGGAGACAACCCTAACAGCAGTGACTATCCGGCACCAAGAGCCGTCCTCACAGGCCATGACCATGAAGTTGTCTGTGTTTCTGTCTGTGCAGAACTTGGGCTTGTTATCAGTGGTGCTAAAGAGGGCCCTTGCCTTGTCCACACCATCACTGGAGATTTGCTGAGAGCCCTTGAAGGACCAGAAAACTGCTTATTCCCACGCTTGATATCTGTCTCCAGCGAAGGCCACTGTATCATATACTATGAACGAGGGCGATTCAGTAATTTCAGCATTAATGGGAAACTTTTGGCTCAAATGGAGATCAATGATTCAACACGGGCCATTCTCCTGAGCAGTGACGGCCAGAACCTGGTCACCGGAGGGGACAATGGGGTAGTAGAGGTCTGGCAGGCCTGTGACTTCAAGCAACTGTACATTTACCCTGGATGTGATGCTGGCATTAGAGCAATGGACTTGTCCCATGACCAGAGGACTCTGATCACTGGCATGGCTTCTGGTAGCATTGTAGCTTTTAATATAGATTTTAATCGGTGGCATTATGAGCATCAGAACAGATACAGA AGATAAAGGAAGAACCAAAAGCCAAGTTAAAGCTGAGAGCACAAGTGCTGCATGGAAAGGCAATATCTCTGGTGGAAAAAACTCGTCTACATCGACCTCCGTTTGTACATTCCATCACACCCAGCAATAGCTGTACATTGTAGTCAGCAACCATTTTACTTTGTGTGTTTTTTCACGACTGAACACCAGCTGCTATCAAGCAAGCTTATATCATGTAAATTATATGAATTAGGAGATGTTTTGGTAATTATTTCATATATTGTTGTTTATTGAGAAAAGGTTGTAGGATGTGTCACAAGAGACTTTTGACAATTCTGAGGAACCTTGTGTCCAGTTGTTACAAAGTTTAAGCTTTGAACCT ORF Start: ATG at 61    ORF Stop: TGAat 8485 SEQ ID NO: 50           2808 aa   MW at 314093.6kD NOV19a.MASEKPGPGPGLEPQPVGLIAVGAAGGGGGGSGGGGTGGSGMGELRGASGSGSVMLPA CG132414-01Protein SequenceGMINPSVPIRNIRMKFAVLIGLIQVGEVSNRDIVETVLNLLVGGEFDLEMNFIIQDAESITCMTELLEHCDVTCQAEIWSMFTAILRKSVRNLQTSTEVGLIEQVLLKMSAVDDMIADLLVDMLGVLASYSITVKELKLLFSMLRGESGIWPRHAVKLLSVLNQMPQRHGPDTFFNFPGCSAAAIALPPIAKWPYQNGFTLNTWFRMDPLNNINVDKDKPYLYCFRTSKGVGYSAHFVGNCLIVTSLKSKGKGFQHCVKYDFQPRKWYMISIVHIYNRWRNSEIRCYVNGQLVSYGDMAWHVNTNDSYDKCFLGSSETADANRVFCGQLGAVYVFSEALNPAQIFAIHQLGPGYKSTFKFKSESDIHLAEHHKQVLYDGKLASSIAFTYNAKATDAQLCLESSPKENASIFVHSPHALMLQDVKAIVTHSIHSAIHSIGGIQVLFPLFAQLDNRQLNDSQVETTVATLLAFLVELLKSSVAMQEQMLGGKGFLVIGYLLEKSSRVHITRAVLEQFLSFAKYLDGLSHGAPLLKQLCDHILFNPAIWIHTPAKVQLSLYTYLSAEFIGTATIYTTIRRVGTVLQLMHTLKYYYWVINPADSSGITPKGLDGPRPSQKEIISLRAFMLLFLKQLILKDRGVKEDELQSILNYLLTMHEDENIHDVLQLLVALMSEHPASMIPAFDQRNGIRVIYKLLASKSESIWVQALKVLGYFLKHLGHKRKVEIMHTHSLFTLLGERLMLHTNTVTVTTYNTLYEILTEQVCTQVVHKPHPEPDSTVKIQNPMILKVVATLLKNSTPSAELMEVRRLFLSDMIKLFSNSRENRRCLLQCSVWQDWMFSLGYINPKNSEEQKITEMVYNIFRILLYHAIKYEWGGWRVWVDTLSIAHSKVTYEAHKEYKAKMYEEYQRQEEENIKKGKKGNVSTISGLSSQTTGAKGGMEIREIEDLSQSQSPESETDYPVSTDTRDLLMSTKVSDDILGNSDRPGSGVHVEVHDLLVDIKAEKVEATEVKLDDMDLSPETLVGGENGALVEVESLLDNVYSAAVEKLQNNVHGSVGIIKKNEEKDNGPLITLADEKEDLPNSSTSFLFDKIPKQEEKLLPELSSNHIIPNIQDTQVHLGVSDDLGLLAHMTGSVDLTCTSSIIEEKEFKIHTTSDGMSSISERDLASSTKGLEYAEMTATTLETESSSSKIVPNIDAGSIISDTERSDDGKESGKEIRKIQTTTTTQGRSITQQDRDLRVDLGFRGMPMTEEQRRQFSPGPRTTMFRIPEFKWSPMHQRLLTDLLFALETDVHVWRSHSTKSVMDFVNSNENIIFVHNTIHLISQMVDNIIIACGGILPLLSAATSPTGSKTELENIEVTQGMSAETAVTFLSRLMAMVDVLVFASSLNFSEIEAEKNMSSGGLMRQCLRLVCCVAVRNCLECRQRQRDRGNKSSHGSSKPQEVPQSTPLENVPGNLSPIKDPDRLLQDVDINRLRAVVFRDVDDSKQAQFLALAVVYFISVLMVSKYRDILEPQRETTRTGSQPGRNIRQEINSPTSTETPAAFPDTIKEKETPTPGEDIQVESSIPHTDSGIGEEQVASILNGAELETSTGPDAMSELLSTLSSEVKKSQESLTENPSETLKPATSISSISQTKGINVKEILKSLVAAPVEIAECGPEPIPYPDPALKRETQAILPMQFHSFDSITAKLERALEKVAPLLREIFVDFAPFLSRTLLGSHGQELLIEGLVCMKSSTSVVELVMLLCSQEWQNSIQKNAGLAFIELINEGRLLCHAMKDHIVRVANEAEFILNRQRAEDVHKHAEFESQCAQYAADRREEEKMCDHLISAAKHRDHVTANQLKQKILNILTNKHGAWGAVSHSQLHDFWRLDYWEDDLRRRRRFVRNAFGSTHAEALLKAAIEYGTEEDVVKSKKTFRSQAIVNQNAETELMLEGDDDAVSLLQEKEIDNLAGPVVLSTPAQLIAPVVVAKGTLSITTTEIYFEVDEDDSAFKKIDTKVLAYTEGLHGKWMFSEIRAVFSRRYLLQNTALEVFMANRTSVMFNFPDQATVKKVVYSLPRVGVGTSYGLPQARRISLATPRQLYKSSNMTQRWQRREISNFEYLMFLNTIAGRRYNDLNQYPVFPWVLTNYESEELDLTLPGNFRDLSKPIGALNPKRAVFYAERYETWEDDQSPPYHYNTHYSTATSTLSWLVRIEPFTTFFLLSKPIGALNPKRAVFYAERYETWEDDQSPPYHYNTHYSTATSTLSWLVRIEPFTTFFLNANDGKFDHPDRTFSSVARSWRTSQRDTSDVKELIPEFYYLPEMFVNSNGYNLGVREDEVVVNDVDLPPWAKKPEDFVRINRMALESEFVSCQLHQWIDLIFGYKQRGPEAVRALNVFHYLTYEGSVNLDSITDPVLREAMEAQIQNFGQTPSQLLIEPHPPRSSAMHLCFLPQSPLMFKDQMQQDVIMVLKFPSNSPVTHVAANTLPHLTIPAVVTVTCSRLFAVNRWHNTVGLRGAPGYSLDQAHHLPIEMDPLIANNSGVNKRQITDLVDQSIQINAHCFVVTADNRYILICGFWDKSFRVYSTETGKLTQIVFGHWDVVTCLARSESYIGGDCYIVSGSRDATLLLWYWSGRHHIIGDNPNSSDYPAPRAVLTGHDHEVVCVSVCAELGLVISGAKEGPCLVHTITGDLLRALEGPENCLFPRLISVSSEGHCIIYYERGRFSNFSINGKLLAQMEINDSTRAILLSSDGQNLVTGGDNGVVEVWQACDFKQLYIYPGCDAGIRAMDLSHDQRTLITGMASGSIVAFNIDFNRWHYEHQNRY

[0420] Further analysis of the NOV19a protein yielded the followingproperties shown in Table 19B. TABLE 19B Protein Sequence PropertiesNOV19a PSort 0.6000 probability located in plasma membrane; 0.4000analysis: probability located in Golgi body; 0.3000 probability locatedin endoplasmic reticulum (membrane); 0.3000 probability located inmicrobody (peroxisome) SignalP No Known Signal Sequence Predictedanalysis:

[0421] A search of the NOV19a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table19C TABLE 19C Geneseq Results for NOV19a NOV19a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAY32131 HumanLYST-2 protein - Homo 2026 . . . 2808 780/783 (99%) 0.0 sapiens. 789 a.[WO9951741-A2.  7 . . . 789 782/783 (99%) 14 OCT. 1999] AAW23399 MouseLYST2 polypeptide - Mus 2094 . . . 2791 684/698 (97%) 0.0 musculus. 703aa. [WO9728262-  3 . . . 700 692/698 (98%) A1.07 AUG. 1997] AAM39018Human polypeptide SEQ ID NO 2147 . . . 2808 662/662 (100%) 0.0 2163-Homo sapiens. 662 aa.  1 . . . 662 662/662 (100%) [WO200153312-A1. 26JUL. 2001] ABB62664 Drosophila melanogaster 1718 . . . 2808 674/1122(60%) 0.0 polypeptide SEQ ID NO 14784- 2511 . . . 3614 856/1122 (76%)Drosophila melanogaster. 3614 aa. [WO200171042-A2. 27 SEP. 2001]AAY32120 Human LYST-2 protein - Homo 2290 . . . 2761 470/472 (99%) 0.0sapiens 472 aa. [WO9951741-A2.  1 . . . 472 472/472 (99%) 14 OCT. 1999]

[0422] In a BLAST search of public sequence datbases, the NOV19a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 19D. TABLE 19D Public BLASTP Results for NOV19a NOV19a ProteinResidues/ Identities/ Accession Match Similarities for the Expect NumberProtein/Organism/Length Residues Matched Portion Value AAM53531 BCL8Bprotein - Homo 1 . . . 1744 1743/1788 (97%) 0.0 sapiens (Human), 2946aa. 1 . . . 1788 1743/1788 (97%) Q9EPN0 Neurobeachin - Mus musculus 1 .. . 1744 1684/1756 (95%) 0.0 (Mouse), 2904 aa. 1 . . . 1746 1713/1756(96%) Q9EPM9 Neurobeachin - Mus musculus 1 . . . 1744 1684/1788 (94%)0.0 (Mouse), 2931 aa. 1 . . . 1778 1713/1788 (95%) Q9EPN1 Neurobeachin -Mus musculus 1 . . . 1744 1684/1788 (94%) 0.0 (Mouse), 2936 aa. 1 . . .1778 1713/1788 (95%) Q9HCM8 KIAA1544 protein - Homo 1781 . . . 2808   1028/1028 (100%) 0.0 sapiens (Human), 1028 aa 1 . . . 1028  1028/1028(100%) (fragment).

[0423] PFam analysis predicts that the NOV19a protein contains thedomains shown in the Table 19E. TABLE 19E Domain Analysis of NOV19aIdentities/ Similarities NOV19a for the Expect Pfam Domain Match RegionMatched Region Value Beach 2148 . . . 2425 182/287 (63%) 4.9e−208260/287 (91%) WD40 2717 . . . 2752  11/37 (30%) 0.89  29/37 (78%)

Example 20

[0424] The NOV20 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 20A. TABLE 20A NOV20 SequenceAnalysis SEQ ID NO: 51           2687 bp NOV20a.ACAAGCTCCACAGAGCCGCGGGAGGACGGTTGCCTGGTATTATTAGCAAGCAGCAAAT CG133140-01DNA Sequence ATGGCGGTGGCGCGCGTGGACGCGGCTTTGCCTCCCGGAGAAGGTTCAGTGGTCAATTGGTCAGGACAGGGACTACAGAAATTAGGTCCAAATTTACCCTGTGAAGCTGATATTCACACTTTGATTCTGGATAAAAATCAGATTATTAAATTGGAAAATCTGGAGAAATGCAAACGATTAATACAGTTATCAGTAGCTAATAATCGGCTGGTTCGGATGATGGGTGTGGCCAAGCTGACGTTGCTTCGTGTATTAAATTTGCCTCATAATAGCATTGGCTGTGTGGAAGGGCTAAAGGAACTAGTACATCTGGAATGGCTGAATTTGGCAGGAAATAATCTTAAGGCCATGGAACAGATCAATAGCTGCACAGCTCTACAGCATCTCGATTTATCAGACAATAATATATCCCAGATAGGTGATCTATCTAAATTGGTATCCCTGAAAGTAAAGACCCTGCTTTTACATGGAAACATCATCACCTCTCTTAGAATGGCACCTGCTTACCTACCCAGAAGTCTTGCTATACTTTCTTTGGCAGAAAATGAAATCCGAGACTTAAATGAGATCTCTTTTTTGGCATCCTTAACTGAATTGGAACAGTTGTCGATTATGAACAATCCTTGTGTGATGGCAACACCATCCATCCCAGGATTTGACTATCGGCCGTACATCGTCAGCTGGTGCCTAAACCTCAGAGTCCTAGATGGATATGTGATTTCTCAGAAGGAAAGTTTGAAAGCTGAATGGCTCTATAGTCAAGGCAAGGGGAGAGCATATCGGCCTGGCCAGCACATCCAGCTTGTCCAATATCTGGCTACAGTCTGCCCCCTCACTTCTACACTAGGTCTTCAAACTGCAGAGGATGCCAAACTAGACAAGATTTTGAGCAAACAGAGGTTTCACCAGAGGCAGTTGATGAACCAAAGCCAAAATGAAGAGTTGTCTCCTCTTGTTCCTGTTGAAACAAGGGCATCCCTTATTCCTGAGCATTCAAGCCCTGTTCAAGATTGCCAGATATCCGAACCCGTCATTCAAGTGAATTCTTGGGTTGGGATAAACAGTAATGATGATCAGTTATTTGCGGTTAAGAATAATTTTCCAGCCTCTAGTCACACTACGAGATATTCTCGAAATGATCTGCACCTGGAAGACATACAGACGGATGAGGACAAGTTAAACTGTAGTCTTCTCTCTTCAGAGTCTACTTTTATGCCAGTTGCATCAGGACTGTCTCCACTATCACCTACAGTTGAGCTGAGGCTGCAGGGCATTAACTTGGGCCTAGAAGATGATGGTGTTGCAGATGAATCTGTGAAAGGGCTGGAAAGCCAGGTGTTGGATAAGGAAGAGGAACAGCCTTTATGGGCTGCAAATGAGAATTCTGTTCAAATGATGAGAAGTGAAATCAATACAGAGGTAAATGAGAAAGCTGGACTATTACCTTGTCGGTGTTGGATAAGGAAGAGGAACAGCCTTTATGGGCTGCAAATGAGAATTCTGTTCAAATGATGAGAAGTGAAATCAATACAGAGGTAAATGAGAAAGCTGGACTATTACCTTGTCCTGAGCCAACAATAATCAGTGCTATCTTGAAGGATGATAACCACAGTCTTACATTTTTTCCTGAGTCAACTGAGCAGAAACAATCAGACATAAAGAAACCAGAAAATACACAACCAGAAAATAAAGAAACCATATCTCAAGCAACTTCAGAGAAACTTCCCATGATTTTAACCCAGAGATCTGTTGCTTTGGGACAAGACAAAGTTGCCCTTCAGAAATTAAATGATGCAGCCACCAAGCTTCAGGCCTGTTGGCGGGGATTTTATGCCAGGAACTACAACCCTCAAGCCAAAGATGTGCGTTACGAAATCCGGCTACGCAGAATGCAAGAGCACATTGTCTGCTTAACTGATGAAATAAGGAGATTACGAAAAGAAAGAGATGAAGAACGTATTAAAAAATTTGTACAAGAAGAAGCTTTCAGATTCCTTTGGAACCAGGTAAGGTCTCTACAGGTTTGGCAACAGACAGTGGACCAGCGTCTAAGTTCCTGGCATACTGATGTTCAACAAATATCAAGTACTCTTGTGCCATCGAAACATCCATTATTTACCCAAAGCCAGGAGTCCTCTTGTGATCAAAATGCTGATTGGTTTATTGCTTCTGATGTAGCTCCTCAAGAGAAATCATTACCAGAATTTCCAGACTCTGGTTTTCATTCCTCTCTAACAGAACAAGTTCATTCATTGCAGCATTCTTTGGATTTTGAGAAAAGTTCCACAGAAGGCAGTGAAAGCTCCATAATGGGGAATTCCATTGACACAGTCAGATATGGCAAACAATCAGATTTAGGGGATGTTAGTGAAGAACATGGTGAATGGAATAAGGAAAGCTCAAATAACGAGCAGGACAATAGTCTGCTTGAACAGTATTTAACTTCAGTTCAACAGCTGGAAGATGCTGATGAGAGGACCAATTTTGATACAGAGACAAGAGATAGCAAACTTCACATTGCTTGTTTCCCAGTACAGTTAGATACATTGTCTGACGGTGCTTCTGTAGATGAGAGTCATGGCATATCTCCTCCTTTGCAAGGTGAAATTAGCCAGACACAAGAGAATTCTAAATTAAATGCAGAAGTTCAGGGGCAGCAGCCAGAATGTGATTCTACATTTCAGCTATTGCATGTTGGTGTTACTGTGTAG CATGTCTTTTGGGAGGCAGATATCCACTTAACTT ORF Start ATG at 59     ORF Stop: TAG at 265 SEQ IDNO: 52           864 aa    MW at 96898.9kD NOV20a.MAVARVDAALPPGEGSVVNWSGQGLQKLGPNLPCEADIHTLILDKNQIIKLENLEKCK CC133140-0Protein SequenceRLIQLSVANNRLVRMMGVAKLTLLRVLNLPHNSIGCVEGLKELVHLEWLNLAGNNLKAMEQINSCTALQHLDLSDNNISQIGDLSKLVSLKVKTLLLHGNIITSLRMAPAYLPRSLAILSLAENEIRDLNEISFLASLTELEQLSIMNNPCVMATPSIPGFDYRPYIVSWCLNLRVLDGYVISQKESLKAEWLYSQGKGRAYRPGQHIQLVQYLATVCPLTSTLGLQTAEDAKLDKILSKQRFHQRQLMNQSQNEELSPLVPVETRASLIPEHSSPVQDCQISEPVIQVNSWVGINSNDDQLFAVKNNFPASSHTTRYSRNDLHLEDIQTDEDKLNCSLLSSESTFMPVASGLSPLSPTVELRLQGINLGLEDDGVADESVKGLESQVLDKEEEQPLWAANENSVQMMRSEINTEVNEKAGLLPCPEPTIISAILKDDNHSLTFFPESTEQKQSDIKKPENTQPENKETISQATSEKLPMILTQRSVALGQDKVALQKLNDAATKLQACWRGFYARNYNPQAKDVRYEIRLRRMQEHIVCLTDEIRRLRKERDEERIKKFVQEEAFRFLWNQVRSLQVWQQTVDQRLSSWHTDVQQISSTLVPSKHPLFTQSQESSCDQNATWFIASDVAPQEKSLPEFPDSGFHSSLTEQVHSLQHSLDFEKSSTEGSESSIMGNSIDTVRYGKESDLGDVSEERGEWNKESSNNEQDNSLLEQYLTSVQQLEDADERTNFDTETRDSKLHIACFPVQLDTLSDGASVDESHGISPPLQGEISQTQENSKLNAEVQGQQPECDSTFQLLHVGVTV

[0425] Further analysis of the NOV20a protein yielded the followingproperties shown in Table 20B. TABLE 20B Protein Sequence PropertiesNOV20a PSort 0.4500 probability located in cytoplasm; 0.3000 analysis:probability located in microbody (peroxisome); 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probability located inlysosome (lumen) SignalP No Known Signal Sequence Predicted analysis:

[0426] A search of the NOV20a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table20C. TABLE 20C Geneseq Results for NOV20a NOV20a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length[Patent Match theMatched Expect Identifier #, Date] Residues Region Value ABB60319Drosophila melanocaster  14 . . . 636 206/648 (31%) e−77 polypeptide SEQID NO 7749 -  9 . . . 625 330/648 (50%) Drosophila melanogaster. 774 aa.[WO200171042-A2. 27 SEP. 2001] AAM25487 Human protein sequence SEQ ID  1. . . 129 128/129 (99%) 5e−68 NO:1002 - Homo sapiens. 133 aa.  5 . . .133 128/129 (99%) [WO200153455-A2. 26 JUL. 2001] AAG03667 Human secretedprotein. SEQ ID  1 . . . 129 127/129 (98%) 3e−67 NO: 7748- Homo sapiens.129 aa.  1 . . . 129 127/129 (98%) [EP1033401-A2. 06 SEP. 2000] AAY12286Human 5′ EST secreted protein SEQ  73 . . . 130 57/58 (98%) 6e−26 IDNO:317 - Homo sapiens. 58 aa.  1 . . . 58 57/58 (98%) [WO9906548-A2. 11FEB. 1999] ABG12142 Novel human diagnostic protein 189 . . . 245 56/57(98%) 1e−25 #12133 - Homo sapiens. 422 aa. 109 . . . 165 57/57 (99%)[WO200175067-A2. 11 OCT. 200I]

[0427] In a BLAST search of public sequence datbases, the NOV20a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 20D. TABLE 20D Public BLASTP Results for NOV20a NOV20a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9CZ622810403B08Rik protein - Mus 1 . . . 864 658/865 (76%) 0.0 musculus(Mouse), 856 aa. 1 . . . 853 729/865 (84%) Q9VQV7 CG3980 protein -Drosophila 14 . . . 636  206/648 (31%) 4e−77 melanogaster (Fruit fly),774 aa. 9 . . . 625 330/648 (50%) Q9H5T9 CDNA: FLJ23047 fis, clone 732 .. . 864  132/133 (99%) 4e−69 LNG02513 - Homo sapiens 1 . . . 132 132/133(99%) (Human), 132 aa. O16366 R02F11.4 protein - 60 . . . 300   72/242(29%) 1e−20 Caenorhabditis elegans, 630 aa. 122 . . . 336  113/242 (45%)Q09589 Hypothetical 136.6 kDa protein - 34 . . . 207   59/174 (33%)1e−14 Caenorhabditis elegans, 1223 aa. 30 . . . 196   91/174 (51%)

[0428] PFam analysis predicts that the NOV20a protein contains thedomains shown in the Table 20E. TABLE 20E Domain Analysis of NOV20aIdentities/ Similarities NOV20a for the Expect Pfam Domain Match RegionMatched Region Value LRR 125 . . . 146  9/25 (36%) 0.0098 19/25 (76%) IQ558 . . . 578 10/21 (48%) 0.05 16/21 (76%)

Example 21

[0429] The NOV21 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 21A. TABLE 21A NOV21 SequenceAnalysis SEQ ID NO: 53           3222 bp NOV21a.TTCAGCCCTGAGAATTTTGAGCCACATTTGTTGCTATTATTTTTGCATGCACTTTTCA CG133369-01DNA Sequence AA ATGATTGACTTAAGCTTCCTGACTGAAGAGGAACAAGAGGCCATCATGAAGGTTTTGCAGCGGGATGCTGCTCTGAAGAGGGCCGAAGAAGAGAGAGTCAGACATTTGCCTGAAAAAATTAAGGATGACCAGCAGCTGAAGAATATGAGTGGCCAATGGTTTTATGAAGCCAAGGCAAAAAGGCACAGGGACAAAATCCATGGCGCAGATATCATCAGAGCATCTATGAGAAAGAAGAGGCCCCAGATAGCAGCTGAGCAGAGTAAAGACAGAGAAAATGGGGCAAAGGAAAGCTGGGTGAATAATGTCAACAAAGATGCTTTCCTTCCTCCAGAGCTGGCTGGCGTTGTAGAAGAGCCAGAAGAAGATGCAGCACCAGCAAGCCCGAGTTCCAGTGTGGTAAATCCAGCTTCCAGTGTGATTGATATGTCCCAGGAAAACACAAGGAAACCAAATGTGTCTCCAGAGAAGCAGAGGAAGAATCCGTTTAATAGCTCCAAGTTGCCAGAAGGTCACTCATCACAACAAACTAAAAATGAACAGTCAAAAAATGGAAGAACTGGTTTATTTCAGACTTCAAAAGAGGATGAATTGTCAGAGTCAAAAGAAAAGTCAACTGTCGCAGATACTTCAATCCAAAAGTTAGAGAAATCAAAGCAGACTTTGCCAGGCCTTTCAAATGGGTCCCAAATCAAGGCTCCAATCCCCAAAGCCAGGAAGATGATCTACAAATCAACTGATTTAAACAAAGATGATAACCAGTCTTTTCCTAGACAAAGGACAGACTCCCTGAAAGCGAGAGGGGCTCCGAGAGGGATCCTCAAGCGCAACTCCAGTTCCAGTAGCACAGACTCAGAAACCCTTCGTTATAATCACAACTTTGAACCCAAAAGCAAAATTGTGTCACCTGGCCTAACCATCCATGAGAGAATTTCTGAGAAGGAGCATTCTTTAGAAGACAACTCTTCCCCAAACTCCCTGGAGCCATTAAAGCATGTGAGATTCTCTGCAGTGAAGGATGAGCTTCCACAGAGTCCTGGGCTAATCCATGGTCGGGAAGTAGGAGAATTTAGTGTTTTAGAATCTGACAGATTGAAAAATGGAATGGAAGATGCAGGGGACACAGAAGAGTTTCAGAGTGACCCTAAGCCTTCTCAATACAGAAAGCCTTCGCTTTTTCATCAATCAACCTCAAGCCCATATGTATCAAAAAGTGAAACACATCAGCCAATGACTTCTGGTTCTTTTCCAATTAATGGGCTGCATTCTCATTCAGAAGTTTTAACTGCAAGACCACAGTCTATGGAGAATTCACCAACCATCAATGAACCCAAAGATAAATCATCAGAATTAACAAGGCTTGAATCTGTATTACCCAGAAGCCCTGCTGATGAACTGTCTCATTGTGTTGAGCCTGAGCCATCTCAGGTGCCAGGTGGCAGTTCTAGAGACCGTCAGCAAGGTTCAGAAGAAGAACCCAGTCCTGTTTTGAAAACTTTGGAAAGGAGTGCCGCTAGGAAAATGCCTTCCAAAAGTCTAGAAGACATTTCATCAGATTCATCAAATCAAGCAAAAGTAGATAATCAGCCAGAAGAATTAGTGCGTAGTGCTGAAGATGATGAGAAACCAGATCAGAAGCCAGTTACAAATGAATGCGTACCAAGAATTTCCACAGTGCCTACACAACCTGATAATCCATTTTCTCACCCTGACAAACTCAAAAGGATGAGCAAGTCTGTTCCAGCATTTCTCCAAGATGAGGCAGATGACAGAGAAACAGATACAGCATCAGAAAGCAGTTACCAGCTCAGCAGACACAAGAAGAGCCCGAGCTCTTTAACCAATCTTAGCAGCTCCTCTGGCATGACGTCCTTGTCTTCTGTGAGTGGCAGTGTGATGAGTGTTTATAGTGGAGACTTTGGCAATCTGGAAGTTAAAGGAAATATTCAGTTTGCAATTGAATATGTGGAGTCACTGAAGGAGTTGCATGTTTTTGTGGCCCAGTGTAACGACTTAGCAGCAGCGGATGTAAAAAAACAGCGTTCAGACCCATATGTAAAGGCCTATTTGCTACCAGACAAAGGCAAAATGGGCAAGAAGAAAACACTCGTAGTGAAGAAAACCTTGAATCCTGTGTATAACGAAATACTGCGGTATAAAATTGAAAAACAAATCTTAAAGACACAGAAATTGAACCTGTCCATTTGGCATCGGGATACATTTAAGCGCAATAGTTTCCTAGGGGAGGTGGAACTTGATTTGGAAACATGGGACTGGGATAACAAACAGAATAAACAATTGAGATGGTACCCTCTGAAGCGGAAGACAGCACCAGTTGCCCTTGAAGCAGAAAACAGAGGTGAAATGAAACTAGCTCTCCAGTATGTCCCAGAGCCAGTCCCTGGTAAAAAGCTTCCTACAACTGGAGAAGTGCACATCTGGGTGAAGGAATGCCTTGATCTACCACTGCTAAGGGGAAGTCATCTAAATTCTTTTGTTAAATGTACCATCCTTCCAGATACAAGTAGGAAAAGTCGCCAGAAGACAAGAGCTGTAGGGAAAACCACCAACCCTATCTTCAACCACACTATGGTGTATGATGGGTTCAGGCCTGAAGATCTGATGGAAGCCTGTGTAGAGCTTACTGTCTGGGACCATTACAAATTAACCAACCAATTTTTGGGAGGTCTTCGTATTGGCTTTGGAACAGGTAAAAGTTATGGGACTGAAGTGGACTGGATGGACTCTACTTCAGAGGAAGTTGCTCTCTGGGAGAAGATGGTAAACTCCCCCAATACTTGGATTGAAGCAACACTGCCTCTCAGAATGCTTTTGATTGCCAAGATTTCCAAATCA GCCCAAATTCCATCTGGCTCCTCCACTGAAAACTACTAAACCGGTGGAATCTGATCTTGAAAATCTGAGTAGGTGGACAAATATCCTCACTTTCTATCTATTGCACCTAAGGAATACTACACAGCATGTAAAAGTCAATCTGCATGTGCTTCTTTGATTACAAGGCCCAAGGGATTTAAATATAACAAAATGTGTAATTTGTGACTCTAATATTAAATAAGATATTTGAACAAGCTAGGAAAATTGAATTTCTGCTGCTGCTTCAAAGAAAAAGCTGCCCCAGAGCATTAAACATGGGGTATTGTTA ORF Start: ATG at 61    ORF Stop: TGAat 2914 SEQ ID NO 54            951 aa    MW at 106892.0kD NOV21a.MIDLSFLTEEEQEAIMKVLQRDAALKRAEEERVRHLPEKIKDDQQLKNMSGQWFYEAK CG133369-01Protein SequenceAKRHRDKIHGADIIRASMRKKRPQIAAEQSKDRENGAKESWVNNVNKDAFLPPELAGVVEEPEEDAAPASPSSSVVNPASSVIDMSQENTRKPNVSPEKQRKNPFNSSKLPEGHSSQQTKNEQSKNGRTGLFQTSKEDELSESKEKSTVADTSIQKLEKSKQTLPGLSNGSQIKAPIPKARKMIYKSTDLNKDDNQSRPRQRTDSLKARGAPRGILKRNSSSSSTDSETLRYNHNFEPKSKIVSPGLTIHERISEKEHSLEDNSSPNSLEPLKHVRFSAVKDELPQSPGLTHGREVGEFSVLESDRLKNGMEDAGDTEEFQSDPKPSQYRKPSLFHQSTSSPYVSKSETHQPMTSGSFPINGLHSHSEVLTARPQSMENSPTINEPKDKSSELTRLESVLPRSPADELSHCVEPEPSQVPGGSSRDRQQGSEEEPSPVLKTLERSAARKMPSKSLEDISSDSSNQAKVDNQPEELVRSAEDDEKPDQKPVTNECVPRISTVPTQPDNPFSHPDKLKRMSKSVPAFLQDEADDRETDTASESSYQLSRHKKSPSSLTNLSSSSGMTSLSSVSGSVMSVYSGDFGNLEVKGNIQFAIEYVESLKELHVFVAQCKDLAAADVKKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKEIKQILKTQKLNLSIWHRDTFKRNSFLGEVELDLETWDWDNKQNKQLRWYPLKRKTAPVALEAENRGEMKLALQYVPEPVPGKKLPTTGEVHIWVKECLDLPLLRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYDGFRPEDLMEACVELTVWDHYKLTNQFLGGLRIGFGTGKSYGTEVDWMDSTSEEVALWEKMVNSPNTWIEATLPLRMLLIAKISK

[0430] Further analysis of the NOV21a protein yielded the followingproperties shown in Table 21B. TABLE 21B Protein Sequence PropertiesNOV21a PSort 0.7000 probability located in nucleus; 0.3000 probabilityanalysis: located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located in lysosome(lumen) SignalP No Known Signal Sequence Predicted analysis:

[0431] A search of the NOV21a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table21C. TABLE 21C Geneseq Results for NOV21a NOV21a Identities/ Residues/Similarities for Geneseq Protein/Organisim/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value ABB11731 Humangranuphilin-a homologue, 521..951 410/431 (95%) 0.0 SEQ ID NO 2101—Homosapiens,   1..415 415/431 (96%) 415 aa. [WO200157188-A2, 09- AUG-2001]AAU19725 Human novel extracellular matrix 522..951 390/430 (90%) 0.0protein, Seq ID No 375—Homo  18..407 390/430(90%) sapiens, 407 aa.[WO200155368- A1, 02-AUG-2001] AAM93772 Human polypeptide, SEQ ID NO:576..951 375/376 (99%) 0.0 3778—Homo sapiens, 376 aa.   1..376 376/376(99%) [EP1130094-A2, 05-SEP-2001] AAU87550 Novel central nervous system626..951 326/326 (100%) 0.0 protein #460—Homo sapiens, 348  23..348326/326 (100%) aa. [WO200155318-A2, 02-AUG- 2001] AAU19852 Human novelextracellular matrix 626..951 326/326 (100%) 0.0 protein, Seq ID No502—Homo  23..348 326/326 (100%) sapiens, 348 aa. [WO200155368- A1,02-AUG-2001]

[0432] In a BLAST search of public sequence datbases, the NOV21a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 21D. TABLE 21D Public BLASTP Results for NOV21a Identities/ NOV21aSimilarities Protein Residues/ for the Accession Match Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9HCH5 KIAA1597protein - Homo sapiens (Human). 13 . . . 951  897/939 (95%) 0.0 913 aa(fragment). 16 . . . 913  897/939 (95%) Q99N56 Synaptotagmin-likeprotein 2-a - 1 . . . 951 781/952 (82%) 0.0 Mus musculus (Mouse). 950aa. 1 . . . 950 845/952 (88%) Q99N51 Synaptotagmin-like protein 2-adelta 1 . . . 951 770/952 (80%) 0.0 2S-II - Mus musculus (Mouse). 934aa. 1 . . . 934 832/952 (86%) Q99N52 Synaptotagmin-like protein 2-adelta 1 . . . 951 759/952 (79%) 0.0 2S-I - Mus musculus (Mouse). 923 aa.1 . . . 923 821/952 (85%) Q9NXMI CDNA FLJ20I63 fis. clone COL09380 - 1 .. . 463 462/463 (99%) 0.0 Homo sapiens (Human). 471 aa. 1 . . . 462462/463 (99%)

[0433] PFam analysis predicts that the NOV21a protein contains thedomains shown in the Table 21E. TABLE 21E Domain Analysis of NOV21aIdentities/ Similarities NOV21a for the Expect Pfam Domain Match RegionMatched Region Value C2 662 . . . 751 38/97 (39%) 8.2e−21 65/97 (67%) C2811 . . . 898 23/97 (24%) 4.2e−11 65/97 (67%)

Example 22

[0434] The NOV22 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 22A. TABLE 22A NOV22 SequenceAnalysis SEQ ID NO: 55 2478 bp NOV22a,ACTAGTAAAAAAAGAAAAAGAAAAAATAAAGTGAAAGAGGCGTGTTGTCTAGTTTCAA CG133456-01DNA Sequence AGGAGAGGAGAGAAGGCAACTCTGGTAGCTCTCCTTGTCTCGTTGTTTTGAAGAAAGAAGAGTAGAAGAAAAAGTTGAGTAAATC ATGTCGGAGTTACTGGACCTTTCTTTTCTGTCTGAGGAGGAAAAGGATTTGATTCTCAGTGTTCTACAGCGAGATGAAGAGGTCCGGAAAGCAGATGAGAAAAGGATTAGGCGACTAAAGAATGAGTTACTGGAGATAAAAAGGAAAGGGGCCAAGAGGGGCAGCCAACACTACAGTGATCGGACCTGTGCCCGGTGCCAGGAGAGCCTGGGCCGTTTGAGTCCCAAAACCAATACTTGTCGGGGTTGTAATCACCTGGTGTGTCGGGACTGCCGCATACAGGAAAGCAATGGTACCTGGAGGTGCAAGGTGTGCGCCAAGGAAATAGAGTTGAAGAAAGCAACTGGGGACTGGTTTTATGACCAGAAAGTGAATCGCTTTGCTTACCGCACAGGTAGTGAGATAATCAGGATGTCCCTGCGCCACAAACCTGCAGTGAGTAAAAGAGAGACAGTGGGACAGTCCCTCCTTCATCAGACACAGATGGGTGACATCTGGCCAGGAAGAAAGATCATTCAGGAGCGGCAGAAGGAGCCCAGTGTGCTATTTGAAGTGCCAAAGCTGAAAAGTGGAAAGAGTGCATTGGAAGCTGAGAGTGAGAGTCTGGATAGCTTCACAGCTGACTCGGATAGCACCTCCAGGAGAGACTCTCTGGATAAATCTGGCCTCTTTCCAGAATGGAAGAAGATGTCTGCTCCCAAATCTCAAGTAGAAAAGGAAACTCAGCCTGGAGGTCAAAATGTGGTATTTGTGGATGAGGGTGAGATGATATTTAAGAAGAACACCAGAAAAATCCTCAGGCCTTCAGAGTACACTAAATCTGTGATAGATCTTCGCCCAGAAGATGTGGTACATGAAAGTGGCTCCTTGGGAGACAGAAGCAAATCCGTCCCAGGCCTCAATGTGGATATGGAAGAGGAAGAAGAAGAAGAAGACATTGACCACCTAGTGAAGTTACATCGCCAGAAGCTAGCCAGAAGCAGCATGCAAAGTGGCTCCTCCATGAGTACGATCGGCAGCATGATGAGCATCTACAGTGAAGCTGGTGATTTCGGGAACATCTTTGTGACTGGCAGGATTGCCTTTTCCCTGAAGTATGAGCAGCAAACCCAGAGTCTGGTTGTCCATGTGAAGGAGTGCCATCAGCTGGCCTATGCTGATGAAGCCAAGAAGCGCTCTAACCCATATGTGAAGACTTACCTTCTGCCTGACAAGTCCCGCCAAGGAAAAAGAAAAACCAGCATCAAGCGGGACACTATTAATCCACTATATGATGAGACGCTGAGGTATGAGATCCCAGAATCTCTCCTGGCCCAGAGGACCCTGCAGTTCTCAGTTTGGCATCATGGTCGTTTTGGCAGAAACACTTTCCTTGGAGAGGCAGAGATCCAGATGGATTCCTGGAAGCTTGATAAGAAACTGGATCATTGCCTCCCTTTACATGGAAAGATCAGTGCTGAGTCCCCGACTGGCTTGCCATCACACAAAGGCGAGTTGGTGGTTTCATTGAAATACATCCCAGCCTCCAAAACCCCTGTTGGAGGTGACCGGAAAAAGAGTAAAGGTGGGGAAGGGGGAGAGCTCCAGGTGTGGATCAAAGAAGCCAAGAACTTGACGGCTGCCAAAGCAGGAGGGACTTCAGACAGCTTTGTCAAGGGATACCTCCTTCCCATGAGGAACAAGGCCAGTAAACGTAAAACTCCTGTGATGAAGAAGACCCTGAATCCTCACTACAACCATACATTTGTCTACAATGGTGTGAGGCTGGAAGATCTACAGCATATGTGCCTGGAACTGACTGTGTGGGACCGGGAGCCCCTGGCCAGCAATGACTTCCTGGGAGGGGTCAGGCTGGGTGTTGGCACTGGGATCAGTAATGGGGAAGTGGTGGACTGGATGGACTCGACTGGGGAAGAAGTGAGCCTGTGGCAGAAGATGCGACAGTACCCAGGGTCTTGGGCAGAAGGGACTCTGCAGCTCCGTTCCTCAATGGCCAAGCAGAA GCTGGGTTTATGAGTCCCTGTCCTCTTCTGCAGGTCCAGCCCTGGCGAGGGCAGGTCAGAGGAAGTGAAGAAATCAAGAGCAAAGATTTATAATTTAATGTGTATGTGTGTATGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTACAAACATGTATTTTCTGCAAATCTCATTATGCTGGCTAGAGTGATGCAGACTTGTTCTTCTTTTTAAAGCAGTCTCAAGAATAAGCATTTCTTTAAAATGTTTCTGTGTATAATCTAGTTTATTTTCAGAGTCCATTTTTTCTTATGTCTTTATAAGGTTCACTTAACTTAAAAACAGT ORF Start: ATG at 144 ORFStop: TGA at 2157 SEQ ID NO: 56 671 aa MW at 76022.8kD NOV22aMSELLDLSFLSEEEKDLILSVLQRDEEVRKADEKRIRRLKNELLEIKRKGAKRGSQHY CG133456-01Protein SequenceSDRTCARCQESLGRLSPKTNTCRGCNHLVCRDCRIQESNGTWRCKVCAKEIELKKATGDWFYDQKVNRFAYRTGSEIIRMSLRHKPAVSKRETVGQSLLHQTQMGDIWPGRKIIQERQKEPSVLFEVPKLKSGKSALEAESESLDSFTADSDSTSRRDSLDKSGLFPEWKKMSAPKSQVEKETQPGGQNVVFVDEGEMIFKKNTRKILRPSEYTKSVIDLRPEDVVHESGSLGDRSKSVPGLNVDMEEEEEEEDIDHLVKLHRQKLARSSMQSGSSMSTIGSMMSIYSEAGDFGNIFVTGRIAFSLKYEQQTQSLVVHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETLRYEIPESLLAQRTLQFSVWHHGRFGRNTFLGEAEIQMDSWKLDKKLDHCLPLHGKISAESPTGLPSHKGELVVSLKYIPASKTPVGGDRKKSKGGEGGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLNPHYNHTFVYNGVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGTGISNGEVVDWMDSTGEEVSLWQKMRQYPGSWAEGTLQLRSSMAKQKLGL

[0435] Further analysis of the NOV22a protein yielded the followingproperties shown in Table 22B. TABLE 22B Protein Sequence PropertiesNOV22a PSort 0.8800 probability located in nucleus; 0.1000 probabilityanalysis: located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0436] A search of the NOV22a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table22C. TABLE 22G Geneseq Results for NOV22a NOV22a Identities/ Residues/Similarities for Geneseq Protein/Organisim/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAE17496 Humansecretion and trafficking   1..671 670/671 (99%) 0.0 protein-5(SAT-5)—Homo sapiens,   1..671 671/671 (99%) 671 aa. [WO200202610-A2,10- JAN-2002] AAU87541 Novel central nervous system 378..603 224/226(99%) e−132 protein #451—Homo sapiens, 234   2..227 226/226 (99%) aa.[WO200155318-A2, 02-AUG- 2001] AAU87238 Novel central nervous system378..603 224/226(99%) e−132 protein #148—Homo sapiens, 234   2..227226/226 (99%) aa. [WO200155318-A2, 02-AUG- 2001] AAU19717 Human novelextracellular matrix 378..603 224/226 (99%) e−132 protein, Seq ID No367—Homo   2..227 226/226 (99%) sapiens, 234 aa. [WO200155368- A1,02-AUG-2001] AAM94291 Human reproductive system related 378..603 224/226(99%) e−132 antigen SEQ ID N0: 2949—Homo   2..227 226/226 (99%) sapiens,234 aa. [WO200155320- A2, 02-AUG-2001]

[0437] In a BLAST search of public sequence datbases, the NOV22a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 22D. TABLE 22D Public BLASTP Results for NOV22a NOV22a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q96C24 Similar tosynaptotagmin-like 4 - 1 . . . 671 670/671 (99%) 0.0 Homo sapiens(Human), 671 aa. 1 . . . 671 671/671 (99%) Q8VHQ7 Granuphilin A - Rattusnorvegicus 1 . . . 671 615/672 (91%) 0.0 (Rat), 672 aa. 1 . . . 672643/672 (95%) Q9R0Q1 Granuphilin-a - Mus musculus 1 . . . 671 608/673(90%) 0.0 (Mouse), 673 aa. 1 . . . 673 640/673 (94%) Q9H4R1BA524D16A.2.1 (Novel protein 181 . . . 671   491/491 (100%) 0.0 similarto mouse granuphilin-a) - 1 . . . 491  491/491 (100%) Homo sapiens(Human), 491 aa (fragment). Q8VHQ6 Granuphilin B - Rattus norvegicus 1 .. . 483 436/484 (90%) 0.0 (Rat), 501 aa. 1 . . . 484 460/484 (94%)

[0438] PFam analysis predicts that the NOV22a protein contains thedomains shown in the Table 22E. TABLE 22E Domain Analysis of NOV22aIdentities/ Similarities Pfam Domain NOV22a Match Region for the MatchedRegion Expect Value PHD  62 . . . 108 11/53 (21%) 0.97 28/53 (53%)zf-MIZ  80 . . . 111 13/53 (25%) 0.4 21/53 (40%) RPH3A_effector  1 . . .237 61/318 (19%)  0.035 101/318 (32%)  C2 373 . . . 462 36/97 (37%)8.6e−25 71/97 (73%) C2 528 . . . 617 37/97 (38%) 2.6e−24 71/97 (73%)

Example 23

[0439] The NOV23 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 23A. TABLE 23A NOV23 SequenceAnalysis SEQ ID NO: 57 5993 bp NOV23a.GAGCGCGCCGTCCTCGAGTCCCCGAGCCGCGGAGCCCGCCCGCGCCCCTCGGGCCGCC CG133903-01DNA Sequence CCGCGTCCCTCGCC ATGGCGCGGCTCGCGGACTACTTCGTGCTGGTGGCGTTCGGGCCGCACCCGCGCGGGAGTGGGGAAGGCCAGGGCCAGATTCTGCAGCGCTTCCCAGAGAAGGACTGGGAGGACAACCCATTCCCCCAGGGCATCGAGCTGTTTTGCCAGCCCAGCGGGTGGCAGCTGTGTCCCGAGAGGAATCCACCGACCTTCTTTGTTGCTGTCCTCACCGACATCAACTCCGAGCGCCACTACTGCGCCTGCTTGACCTTCTGGGAGCCAGCGGAGCCTTCACAGGAAACGACGCGCGTGGAGGATGCCACAGAGAGGGAGGAAGAGGGGGATGAGGGAGGCCAGACCCACCTGTCTCCCACAGCACCTGCCCCATCTGCCCAGCTGTTTGCACCGAAGACGCTGGTACTGGTGTCGCGACTCGACCACACGGAGGTGTTCAGGAACAGCCTTGGCCTCATCTATGCCATCCACGTGGAGGGCCTGAATGTGTGCCTGGAGAACGTGATTGGGAACCTGCTGACGTGCACTGTGCCCCTGGCTGGGGGCTCGCAGAGGACGATCTCTTTGGGGGCTGGTGACCGGCAGGTCATCCAGACTCCACTGGCCGACTCGCTGCCCGTCAGCCGCTGCAGCGTGGCCCTGCTCTTCCGCCAGCTAGGCATCACCAACGTGCTGTCTTTGTTCTGTGCCGCCCTCACGGAGCACAAGGTTCTCTTCCTGTCCCGGAGCTACCAGCGGCTCGCCGATGCCTGTAGGGGCCTCCTGGCACTGCTGTTTCCTCTCAGATACAGCTTCACCTATGTGCCCATCCTGCCGGCTCAGCTGCTGGAGGTCCTCAGCACACCCACGCCCTTCATCATTGGGGTCAACGCGGCCTTCCAGGCAGAGACCCAGGAGCTGCTCGATGTGATTGTTGCTGATCTGGATGGAGGGACGGTCACCATTCCTGAGTGTGTGCACATTCCACCCTTGCCAGAGCCACTGCAGAGTCAGACGCACAGTGTGCTGAGCATGGTCCTGGACCCGGAGCTGGAGTTGGCTGACCTCGCCTTCCCTCCGCCCACGACATCCACCTCCTCCCTGAAGATGCAGGACAAGGAGCTGCGCGCGGTCTTCCTGCGGCTGTTCGCTCAGCTGCTGCAGGGCTATCGCTGGTGCCTGCACGTCGTGCGCATCCACCCGGAGCCTGTCATCCGCTTCCATAAGGCAGCCTTCCTGGGGCAGCGTGGGCTGGTAGAGGACGATTTCCTGATGAAGGTGCTGGAGGGCATGGCCTTTGCTGGCTTTGTGTCAGAGCGTGGGGTCCCATACCGCCCTACGGACCTGTTCGATGAGCTGGTGGCCCACGAGGTGGCAAGGATGCGGGCGGATGAGAACCACCCCCAGCGTGTCCTGCGTCACGTCCAGGAACTGGCAGAGCAGCTCTACAAGAACGAGAACCCGTACCCAGCCGTGGCGATGCACAAGGTACAGAGGCCCGGTGAGAGCAGCCACCTGCGACGGGTGCCCCGACCCTTCCCCCGGCTGGATGAGGGCACCGTGCAGTGGATCGTGGACCAGGCTGCAGCCAAGATGCAGGGTGCACCCCCAGCTGTGAAGGCCGAGAGGAGGACCACCGTGCCCTCAGGGCCCCCCATGACTGCCATACTGGAGCGGTGCAGTGGGCTGCATGTCAACAGCGCCCGGCGGCTGGAGGTTGTGCGCAACTGCATCTCCTACGTGTTTGAGGGGAAAATGCTTGAGGCCAAGAAGCTGCTCCCAGCCGTGTTGAGGGCCCTGAAGGGGCGAGTTGCCCGCCGCTGCCTCGCCCAGGAGCTGCACCTGCATGTGCAGCAGAACCGTGCGGTCCTGGACCACCAGCAGTTTGACTTTGTCGTCCGTATGATGAACTGCTGCCTGCAGGACTGCACTTCTCTGGACGAGCATGGCATTGCGGCGGCTCTGCTGCCTCTGGTCACAGCCTTCTGCCGGAAGCTGAGCCCGGGGGTGACGCAGTTTGCATACAGCTGTGTGCAGGAGCACGTGGTGTGGAGCACGCCACAGTTCTGGGAGGCCATGTTCTATGGGGATGTGCAGACTCACATCCGGGCCCTCTACCTGGAGCCCACGGAGGACCTGGCCCCCGCCCAGGAGGTTGGGGAGGCACCTTCCCAGGAGGACGAGCGCTCTGCCCTAGACGTGGCTTCTGAGCAGCGGCGCTTGTGGCCAACTCTGAGTCGTGAGAAGCAGCAGGAGCTGGTGCAGAAGGAGGAGAGCACGGTGTTCAGCCAGGCCATCCACTATGCCAACCGCATGAGCTACCTCCTCCTGCCCCTGGACAGCAGCAAGAGCCGCCTACTTCGGGAGCGTGCCGGGCTGGGCGACCTGGAGAGCGCCAGCAACAGCCTGGTCACCAACAGCATGGCTGGCAGTGTGGCCGAGAGCTATGACACGGAGAGCGGCTTCGAGGATGCAGAGACCTGCGACGTAGCTGGGGCTGTGGTCCGCTTCATCAACCGCTTTGTGGACAAGGTCTGCACGGAGAGTGGGGTCACCAGCGACCACCTCAAGGGGCTGCATGTCATGGTGCCAGACATTGTCCAGATGCACATCGAGACCCTGGAGGCCGTGCAGCGGGAGAGCCGGAGGCTGCCGCCCATCCAGAAGCCCAAGCTGCTGCGGCCGCGCCTGCTGCCGGGTGAGGAGTGTGTGCTGGACGGCCTGCGCGTCTACCTGCTGCCGGATGGGCGTGAGGAGGGCGCGGGGGGCAGTGCTGGGGGACCAGCATTGCTCCCAGCTGAGGGCGCCGTCTTCCTCACCACGTACCGGGTCATCTTCACGGGGATGCCCACGGACCCCCTGGTTGGGGAGCAGGTGGTGGTCCGCTCCTTCCCGGTGGCTGCGCTGACCAAGGAGAAGCGCATCAGCGTCCAGACCCCTGTGGACCAGCTCCTGCAGGACGGGCTCCAGCTGCGCTCCTGCACATTCCAGCTGCTGAAAATGGCCTTTGACGAGGAGGTGGGGTCTGACAGCGCCGAGCTCTTCCGTAAGCAGCTGCATAAGCTGCGGTACCCGCCGGACATCAGGGCCACCTTTGCGTTCACCTTGGGCTCTGCCCACACACCTCGCCGGCCACCGCGAGTCACCAAGGACAAGGGTCCTTCCCTCAGAACCCTGTCCCGGAACCTGGTCAAGAACGCCAAGAAGACCATCGGGCGGCAGCATGTCACTCGCAAGAAGTACAACCCCCCCAGCTGGGAGCACCGGGGCCAGCCGCCCCCTGAGGACCAGGAGGACGAGATCTCAGTGTCGGAGGAGCTGGAGCCCAGCACGCTGACCCCGTCCTCAGCCCTGAAGCCCTCCGACCGCATGACCATGAGCAGCCTGGTGGAAAGGGCTTGCTGTCGCGACTACCAGCGCCTCGGTCTGGGCACCCTGAGCAGCAGCCTGAGCCGGGCCAAGTCTGAGCCCTTCCGCATTTCTCCGGTCAACCGCATGTATGCCATCTGCCGCAGCTACCCAGGGCTGCTGATCGTGCGCCAGAGTGTCCAGGACAACGCCCTGCAGCGCGTGTCCCGCTGCTACCGCCAGAACCGCTTCCCCGTGGTCTGCTGGCGCAGCGGGCGGTCCAAGGCGGTGCTGCTGCGCTCTGGAGGCCTGCATGGCAAAGGTGTCGTCGGCCTCTTCAAGGCCCAGAACGCACCTTCTCCAGGCCAGTCCCAGGCGGACTCGAGTAGCCTGGAGCAGGAGAAGTACCTGCAGGCTGTGGTCAGCTCCATGCCCCGCTACGCCGACGCGTCGGGACGCAACACGCTTAGCGGCTTCTCCTCAGCCCACATGGGCAGTCACGGTAAGTGGGGCAGTGTCCGGACCAGTGGACGCAGCAGTGGCCTTGGCACCGATGTGGGCTCCCGGCTAGCTGGCAGAGACGCGCTGGCCCCACCCCAGGCCAACGGGGGCCCTCCCGACCCGGGCTTCCTGCGTCCGCAGCGAGCAGCCCTCTATATCCTTGGGGACAAAGCCCAGCTCAAGGGTGTGCGGTCAGACCCCCTGCAGCAGTGGGAGCTGGTGCCCATTGAGGTATTCGAGGCACGGCAGGTGAAGGCTAGCTTCAAGAAGCTGCTGAAAGCATGTGTCCCAGGCTGCCCCGCTGCTGAGCCCAGCCCAGCCTCCTTCCTGCGCTCACTGGAGGACTCAGAGTGGCTGATCCAGATCCACAAGCTGCTGCAGGTGTCTGTGCTGGTGGTGGAGCTCCTGGATTCAGGCTCCTCCGTGCTGGTGGGCCTGGAGGATGGCTGGGACATCACCACCCAGGTGGTATCCTTGGTGCAGCTGCTCTCAGACCCCTTCTACCGCACGCTGGAGGGCTTTCGCCTGCTGGTGGAGAAGGAGTGGCTGTCCTTCGGCCATCGCTTCAGCCACCGTGGAGCTCACACCCTGGCCGGGCAGAGCAGCGGCTTCACACCCGTCTTCCTGCAGTTCCTGGACTGCGTACACCAGGTCCACCTGCAGTTCCCCATGGAGTTTGAGTTCAGCCAGTTCTACCTCAAGTTCCTCGGCTACCACCATGTGTCCCGCCGTTTCCGGACCTTCCTGCTCGACTCTGACTATGAGCGCATTGAGCTGGGGCTGCTGTATGAGGAGAAGGGGGAACGCAGGGGCCAGGTGCCGTGCAGGTCTGTGTGGGAGTATGTGGACCGGCTGAGCAAGAGGACGCCTGTGTTCCACAATTACATGTATGCGCCCGAGGACGCAGAGGTCCTGCGGCCCTACAGCAACGTGTCCAACCTGAAGGTGTGGGACTTCTACACTGAGGAGACGCTGGCCGAGGCCCTCCCTATGACTGGGAACTGGCCCAGGGGCCCCCTGAACCCCCAGAGGAAGAACGGTCTGATGGAGGCGTCCCCAGAGCAGCGCCGCGTGGTGTGGCCCTGTTACGACAGCTGCCCGCGGGCCCAGCCTGACGCCATCTCACGCCTGCTGGAGGAGCTGCAGAGGCTGGAGACAGAGTTGGGCCAACCCGCTGAGCGCTGGAAGGACACCTGGGACCGGGTGAAGGCTGCACAGCGCCTCGAGGGCCGGCCAGACGGCCGTGGCACCCCTAGCTCCCTCCTTGTGTCCACCGCACCCCACCACCGTCGCTCGCTGGGTGTGTACCTGCAGGAGGGGCCCGTGGGCTCCACCCTGAGCCTCAGCCTGGACAGCGACCAGAGTAGTGGCTCAACCACATCCGGCTCCCGTCAGGCTGCCCGCCGCAGCACCAGCACCCTGTACAGCCAGTTCCAGACAGCAGAGAGTGAGAACAGGTCCTACGAGGGCACTCTGTACAAGAAGGGGGCCTTCATGAAGCCTTGGAAGGCCCGCTGGTTCGTGCTGGACAAGACCAAGCACCAGCTGCGCTACTACGACCACCGTGTGGACACAGAGTGCAAGGGTGTCATCGACTTGGCGGAGGTGGAGGCTGTGGCACCTGGCACGCCCACTATGGGTGCCCCTAAGACTGTGGACGAGAAGGCCTTCTTTGACGTGAAGACAACGCGTCGCGTTTACAACTTCTGTGCCCAGGACGTGCCCTCGGCCCAGCAGTGGGTGGACCGGATCCAGAGCTGCTGTCGGACGCCTGAGCCTCCCAGCCCTGCCCGGCTGCTCTGCTCTCGTTACCGACCACTAGGGGTGGCAGGGCCGCCCCGGCCATGTTTACAGCCCCGGCCCTCGACAGTACTGAGCCCCGAGCCCCCAGCACTTGTGTGTACAGCCCCCGTCCCCGCCCCGCCCCGCCCGGCCGGCCCTAACTTATTTTGGCGTCACAG CTGAGCACCGTGCCGGGAGGTGGCCAAGGTACAGCCCGCAATGGGCCTGTAAATAGTCCGGCCCCGTCAGCGTGTGCTGGTCCACGGGCTCAGGCGAGTTTCTAGAAAGAGTCTATATAAAGAGAGAACTAACGC ORF Start: ATG at 73 ORF Stop: TGA at 5860 SEQ IDNO: 58 1929 aa MW at 215121.1 kD NOV23a.MARLADYFVLVAFGPHPRGSGEGQGQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCP CG133903-01Protein SequenceERNPPTFFVAVLTDINSERHYCACLTFWEPAEPSQETTRVEDATEREEEGDEGGQTHLSPTAPAPSAQLFAPKTLVLVSRLDHTEVFRNSLGLIYAIHVEGLNVCLENVIGNLLTCTVPLAGGSQRTISLGAGDRQVIQTPLADSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLSTPTPFIIGVNAAFQAETQELLDVIVADLDGGTVTIPECVHIPPLPEPLQSQTHSVLSMVLDPELELADLAFPPPTTSTSSLKMQDKELRAVFLRLFAQLLQGYRWCLHVVRIHPEPVIRFHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSERGVPYRPTDLFDELVAHEVARMRADENHPQRVLRHVQELAEQLYKNENPYPAVAMHKVQRPGESSHLRRVPRPFPRLDEGTVQWIVDQAAAKMQGAPPAVKAERRTTVPSGPPMTAILERCSGLHVNSARRLEVVRNCISYVFEGKMLEAKKLLPAVLRALKGRVARRCLAQELHLHVQQNRAVLDHQQFDFVVRMMNCCLQDCTSLDEHGIAAALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRALYLEPTEDLAPAQEVGEAPSQEDERSALDVASEQRRLWPTLSREKQQELVQKEESTVFSQAIHYANRMSYLLLPLDSSKSRLLRERAGLGDLESASNSLVTNSMAGSVAESYDTESGFEDAETCDVAGAVVRFINRFVDKVCTESGVTSDHLKGLHVMVPDIVQMHIETLEAVQRESRRLPPIQKPKLLRPRLLPGEECVLDGLRVYLLPDGREEGAGGSAGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTPVDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQLHKLRYPPDIRATFAFTLGSAHTPGRPPRVTKDKGPSLRTLSRNLVKNAKKTIGRQHVTRKKYNPPSWEHRGQPPPEDQEDEISVSEELEPSTLTPSSALKPSDRMTMSSLVERACCRDYQRLGLGTLSSSLSRAKSEPFRISPVNRMYAICRSYPGLLIVRQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNAPSPGQSQADSSSLEQEKYLQAVVSSMPRYADASGRNTLSGFSSAHMGSHGKWGSVRTSGRSSGLGTDVGSRLAGRDALAPPQANGGPPDPGFLRPQRAALYILGDKAQLKGVRSDPLQQWELVPIEVFEARQVKASFKKLLKACVPGCPAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGSSVLVGLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQFPMEFEFSQFYLKFLGYHHVSRRFRTFLLDSDYERIELGLLYEEKGERRGQVPCRSVWEYVDRLSKRTPVFHNYMYAPEDAEVLRPYSNVSNLKVWDFYTEETLAEALPMTGNWPRGPLNPQRKNGLMEASPEQRRVVWPCYDSCPRAQPDAISRLLEELQRLETELGQPAERWKDTWDRVKAAQRLEGRPDGRGTPSSLLVSTAPHHRRSLGVYLQEGPVGSTLSLSLDSDQSSGSTTSGSRQAARRSTSTLYSQFQTAESENRSYEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAEVEAVAPGTPTMGAPKTVDEKAFFDVKTTRRVYNFCAQDVPSAQQWVDRIQSCCRTPEPPSPARLLCSRYRPLGVAGPPRPCLQPRPSTVLSPEPPALVCTAPVPAPPRPAGPNLFWRHS

[0440] Further analysis of the NOV23a protein yielded the followingproperties shown in Table 23B. TABLE 23B Protein Sequence PropertiesNOV23a PSort 0.5500 probability located in endoplasmic reticulumanalysis: (membrane); 0.2477 probability located in lysosome (lumen);0.1125 probability located in microbody (peroxisome); 0.1000 probabilitylocated in endoplasmic reticulum (lumen) SignalP No Known SignalSequence Predicted analysis:

[0441] A search of the NOV23a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table23C. TABLE 23C Geneseq Results for NOV23a NOV23a Identities/ Residues/Similarities for Geneseq Protein/Organisim/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value ABB62814Drosophila melanogaster    1..1713  740/1813 (40%) 0.0 polypeptide SEQID NO 15234—    1..1777 1038/1813 (56%) Drosophila melanogaster, 1993aa. [WO200171042-A2, 27-SEP- 2001] AAY96965 Human nucleardual-specificity  969..1862  471/908 (51%) 0.0 phosphatase—Homo sapiens,893    1..888  611/908 (66%) aa. [WO200039277-A2, 06-JUL- 2000] ABG19079Novel human diagnostic protein  726..1345  477/623 (76%) 0.0 #19070—Homosapiens, 1232 aa.  347..918  507/623 (80%) [WO200175067-A2, 11-OCT-2001] ABG19079 Novel human diagnostic protein  726..1345  477/623 (76%)0.0 #19070—Homo sapiens, 1232 aa.  347..918  507/623 (80%)[WO200175067-A2, 11-OCT- 2001] AAM25656 Human protein sequence SEQ ID1397..1862  255/471 (54%) e−142 NO:1171—Homo sapiens, 464 aa.    1..460 322/471 (68%) [WO200153455-A2, 26-JUL- 2001]

[0442] In a BLAST search of public sequence datbases, the NOV23a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 23D. TABLE 23D Public BLASTP Results for NOV23a Identities/Protein NOV23a Similarities for Accession Residues/ the Matched ExpectNumber Protein/Organism/Length Match Residues Portion Value O60228Nuclear dual-specificity 237 . . . 1929 1692/1693 (99%) 0.0phosphatase - Homo sapiens  5 . . . 1697 1693/1693 (99%) (Human), 1697aa (fragment). Q9UGB8 DJ579N16.2 (SET binding factor 237 . . . 18621601/1627 (98%) 0.0 1) - Homo sapiens (Human),  1 . . . 1627 1606/1627(98%) 1631 aa (fragment). Q96GR9 Similar to SET binding factor 1 - 938 .. . 1862  901/926 (97%) 0.0 Homo sapiens (Human), 930 aa  1 . . . 926  906/926 (97%) (fragment). Q9C097 KIAA1766 protein - Homo  30 . . . 1163 713/1141 (62%) 0.0 sapiens (Human), 1123 aa  1 . . . 1122  882/1141(76%) (fragment). Q9VGH9 SBF protein - Drosophila  1 . . . 1713 740/1813 (40%) 0.0 melanogaster (Fruit fly), 1993 aa.  1 . . . 17771038/1813 (56%)

[0443] PFam analysis predicts that the NOV23a protein contains thedomains shown in the Table 23E. TABLE 23E Domain Analysis of NOV23aIdentities/ Similarities NOV23a for the Expect Pfam Domain Match RegionMatched Region Value DENN 171 . . . 310 53/154 (34%) 2.4e−29 92/154(60%) GRAM 882 . . . 968  19/97 (20%) 9.1e−17  68/97 (70%) PH 1761 . . .1864 30/104 (29%) 1.8e−16 76/104 (73%)

Example 24

[0444] The NOV24 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 24A. TABLE 24A NOV24 SequenceAnalysis SEQ ID NO: 59 268O bp NOV24a. TCCGACGCCGTCGCTGGGACCAAGATGGACCTCCCGGCGCTGCTCCCCGCCCCGACTG CG133995-01 DNA SequenceCGCGCGGAGGGCAACATGGCGGCGGCCCCGGCCCGCTCCGCCGAGCCCCAGCGCCGCTCGGCGCGAGCCCCGCGCGCCGCCGCCTGCTACTGGTGCGGGGCCCTGAAGATGGCGGGCCCGGGGCGCGGCCCGGGGAGGCCTCCGGGCCAAGCCCGCCGCCCGCCGAGGACGACAGCGACGGCGACTCTTTCTTGGTGCTGCTGGAAGTGCCGCACGGCGGCGCTGCCGCCGAGGCTGCCGGATCACAGGAGGCCGAGCCTGGCTCCCGTGTCAACCTGGCGAGCCGCCCCGAGCAGGGCCCCAGCGGCCCGGCCGCCCCCCCCGGCCCTGGCGTAGCCCCGGCGGGCGCCGTCACCATCAGCAGCCAGGACCTGCTGGTGCGTCTCGACCGCGGCGTCCTCGCGCTGTCTGCGCCGCCCGGCCCCGCAACCGCGGGCGCCGCCGCTCCCCGCCGCGCGCCCCAGGGCCTCGGCCCCAGCACGCCCGGCTACCGCTGCCCCGAGCCGCAGTGCGCGCTGGCCTTCGCCAAGAAGCACCAGCTCAAGGTGCACCTGCTCACGCACGGCGGCGGTCAGGGCCGGCGGCCCTTCAAGTGCCCACTGGAGGGCTGTGGTTGGGCCTTCACAACGTCCTACAAGCTCAAGCGGCACCTGCAGTCGCACGACAAGCTGCGGCCCTTCGGCTGTCCAGTGGGCGGCTGTGGCAAGAAGTTCACTACGGTCTATAACCTCAAGGCGCACATGAAGGGCCACGAGCAGGAGAGCCTGTTCAAGTGCGAGGTGTGCGCCGAGCGCTTCCCCACGCACGCCAAGCTCAGCTCCCACCAGCGCAGCCACTTCGAGCCCGAGCGCCCTTACAAGTGTGACTTTCCCGGTTGTGAGAAGACATTTATCACAGTGAGTGCCCTGTTTTCCCATAACCGAGCCCACTTCAGGGAACAAGAGCTCTTTTCCTGCTCCTTTCCTGGGTGCACGAGGAAGCAGTATGATAAAGCCTGTCGGCTGAAAATTCACCTGCGGAGCCATACAGGTGAAAGACCATTTATTTGTGACTCTGACAGCTGTGGCTGGACCTTCACCAGCATGTCCAAACTTCTAAGGCACAGAAGGAAACATGACGATGACCGGAGGTTTACCTGCCCTGTCGAGGGCTGTGGGAAATCATTCACCAGAGCAGAGCATCTGAAAGGCCACAGCATAACCCACCTAGGCACAAAGCCGTTCGAGTGTCCTGTGGAAGGATGTTGCGCGAGGTTCTCCGCTCGTAGCAGTCTGTACATTCACTCTAAGAAACACGTGCAGGATGTGGGTGCTCCGAAAAGCCGTTGCCCAGTTTCTACCTGCAACAGACTCTTCACCTCCAAGCACAGCATGAAGGCGCACATGGTCAGACAGCACAGCCGGCGCCAAGATCTCTTACCTCAGCTAGAAGCTCCGAGTTCTCTTACTCCCAGCAGTGAACTCAGCAGCCCAGGCCAAAGTGAGCTCACTAACATGGATCTTGCTGCACTCTTCTCTGACACACCTGCCAATGCTAGTGGTTCTGCAGGTGGGTCGGATGAGGCTCTGAACTCCGGAATCCTGACTATTGACGTCACTTCTGTGAGCTCCTCTCTGGGAGGGAACCTCCCTGCTAATAATAGCTCCCTAGGGCCGATGGAACCCCTGGTCCTGGTGGCCCACAGTGATATTCCCCCAAGCCTGGACAGCCCTCTGGTTCTCGGGACAGCAGCCACGGTTCTGCAGCAGGGCAGCTTCAGTGTGGATGACGTGCAGACTGTGAGTGCAGGAGCATTAGGCTGTCTGGTGGCTCTGCCCATGAAGAACTTGAGTGACGACCCACTGGCTTTGACCTCCAATAGTAACTTAGCAGCACATATCACCACACCGACCTCTTCGAGCACCCCCCGAGAAAATGCCAGTGTCCCGGAACTGCTGGCTCCAATCAAGGTGGAGCCGGACTCGCCTTCTCGCCCAGGAGCAGTTGGGCAGCAGGAAGGAAGCCATGGGCTGCCCCAGTCCACGTTGCCCAGTCCAGCAGAGCAGCACGGTGCCCAGGACACAGAGCTCAGTGCAGGCACTGGCAACTTCTATTTGGAAAGTGGGGGCTCAGCAAGAACTGATTACCGAGCCATTCAACTAGCCAAGGAAAAAAAGCAGAGAGGAGCGGGGAGCAATGCAGGAGCCTCACAGTCTACTCAGAGAAAAATAAAAGAAGGCAAAATGAGTCCTCCCCATTTCCATGCAAGCCAGAACAGTTGGTTGTGTGGGAGCCTCGTGGTGCCCAGCGGAGGACGGCCAGGACCAGCTCCAGCAGCTGGGGTGCAGTGCGGGGCGCAGGGCGTCCAGGTCCAGCTGGTGCAGGATGACCCCTCCGGCGAAGGTGTCCTGCCCTCGGCCCGCGGCCCAGCCACCTTCCTCCCCTTCCTCACTGTGGACCTGCCCGTCTACGTCCTCCAGGAGGTGCTCCCCTCATCTGGAGGCCCTGCTGGACCGGAGGCCACCCAGTTCCCAGGAAGCACTATCAACCTGCAGGATCTGCAGTGA CGGCAGCCTCGGCCTGGGCAGGCCCAAGGCCACGGTCTAGGACACACCTTCCCTGAGACTCATG ACATGAGCCTGGORF Start: ATG at 25 ORF Stop: TGA at 2602 SEQ ID NO: 60 859 aa MW at90169.5 kD NOV24a.MDLPALLPAPTARGGQHGGGPGPLRRAPAPLGASPARRRLLLVRGPEDGGPGARPGEA CG133995-01Protein SequenceSGPSPPPAEDDSDGDSFLVLLEVPHGGAAAEAAGSQEAEPGSRVNLASRPEQGPSGPAAPPGPGVAPAGAVTISSQDLLVRLDRGVLALSAPPGPATAGAAAPRRAPQGLGPSTPGYRCPEPQCALAFAKKHQLKVHLLTHGGGQGRRPFKCPLEGCGWAFTTSYKLKRHLQSHDKLRPFGCPVGGCGKKFTTVYNLKAHMKGHEQESLFKCEVCAERFPTHAKLSSHQRSHFEPERPYKCDFPGCEKTFITVSALFSHNRAHFREQELFSCSFPGCTRKQYDKACRLKIHLRSHTGERPFICDSDSCGWTFTSMSKLLRHRRKHDDDRRFTCPVEGCGKSFTRAEHLKGHSITHLGTKPFECPVEGCCARFSARSSLYIHSKKHVQDVGAPKSRCPVSTCNRLFTSKHSMKAHMVRQHSRRQDLLPQLEAPSSLTPSSELSSPGQSELTNMDLAALFSDTPANASGSAGGSDEALNSGILTIDVTSVSSSLGGNLPANNSSLGPMEPLVLVAHSDIPPSLDSPLVLGTAATVLQQGSFSVDDVQTVSAGALGCLVALPMKNLSDDPLALTSNSNLAAHITTPTSSSTPRENASVPELLAPIKVEPDSPSRPGAVGQQEGSHGLPQSTLPSPAEQHGAQDTELSAGTGNFYLESGGSARTDYRAIQLAKEKKQRGAGSNAGASQSTQRKIKEGKMSPPHFHASQNSWLCGSLVVPSGGRPGPAPAAGVQCGAQGVQVQLVQDDPSGEGVLPSARGPATFLPFLTVDLPVYVLQEVLPSSGGPAGPEATQFPGSTINLQDLQ

[0445] Further analysis of the NOV24a protein yielded the followingproperties shown in Table 24B. TABLE 24B Protein Sequence PropertiesNOV24a PSort 0.9600 probability located in nucleus; 0.3000 probabilityanalysis: located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located in lysosome(lumen) SignalP No Known Signal Sequence Predicted analysis:

[0446] A search of the NOV24a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table24C. TABLE 24C Geneseq Results for NOV24a NOV24a Identities/ Residues/Similarities for Geneseq Protein/Organisim/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAM79014 Humanprotein SEQ ID NO 1676—   1..710 470/816 (57%) 0.0 Homo sapiens, 803 aa.  1..802 527/816 (63%) [WO200157190-A2, 09-AUG- 2001] AAM79998 Humanprotein SEQ ID NO 3644—   1..710 460/811 (56%) 0.0 Homo sapiens, 904 aa.102..903 518/811 (63%) [WO200157190-A2, 09-AUG- 2001] AAB94782 Humanprotein sequence SEQ ID 469..859 391/391 (100%) 0.0 NO:15884—Homosapiens, 391 aa.   1..391 391/391 (100%) [EP1074617-A2, 07-FEB-2001]AAB41289 Human ORFX ORF1053 482..710 229/229 (100%) e−125 polypeptidesequence SEQ ID  11..239 229/229 (100%) NO:2106—Homo sapiens, 240 aa.[WO200058473-A2, 05-OCT- 2000] AAU27665 Human protein AFP162878—753..859 107/107 (100%) 6e−58 Homo sapiens, 107 aa.   1..107 107/107(100%) [WO200166748-A2, 13-SEP-2001]

[0447] In a BLAST search of public sequence datbases, the NOV24a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 24D. TABLE 24D Public BLASTP Results for NOV24a NOV24a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q99J65Hypothetical 80.6 kDa protein - Mus 1 . . . 697 548/711 (77%) 0.0musculus (Mouse), 754 aa. 1 . . . 697 586/711 (82%) P98169 Zinc fingerX-linked protein ZXDB - 1 . . . 710 470/816 (57%) 0.0 Homo sapiens(Human), 803 aa. 1 . . . 802 527/816 (63%) P98168 Zinc finger X-linkedprotein ZXDA - 1 . . . 710 461/807 (57%) 0.0 Homo sapiens (Human), 799aa. 1 . . . 798 522/807 (64%) Q9H891 CDNA FLJ13861 fis. clone 469 . . .859   391/391 (100%) 0.0 THYRO1001100, moderately similar 1 . . . 391 391/391 (100%) to zinc finger X-linked protein ZXDA (Unknown) (Proteinfor MGC:11349) (Hypothetical 39.9 kDa protein) - Homo sapiens (Human),391 aa. 154340 DNA-binding protein - human, 457 211 . . . 661  334/454(73%) 0.0 aa (fragment). 1 . . . 450 371/454 (81%)

[0448] PFam analysis predicts that the NOV24a protein contains thedomains shown in the Table 24E. TABLE 24E Domain Analysis of NOV24aIdentities/ NOV24a Similarities for Expect Pfam Domain Match Region theMatched Region Value zf-C2H2 175 . . . 199 12/25 (48%) 0.0016 18/25(72%) zf-C2H2 208 . . . 232 12/25 (48%) 1.2e−05 22/25 (88%) zf-C2H2 238. . . 262 11/25 (44%) 1.9e−05 22/25 (88%) zf-C2H2 268 . . . 290  8/24(33%) 0.00098 19/24 (79%) zf-C2H2 297 . . . 321 12/25 (48%) 0.0007418/25 (72%) zf-C2H2 359 . . . 383 10/25 (40%) 0.0017 18/25 (72%) zf-C2H2389 . . . 413 13/25 (52%) 1.1e−05 21/25 (84%) zf-C2H2 419 . . . 443 9/25 (36%) 0.37 19/25 (76%) zf-C2H2 452 . . . 477  8/26 (31%) 0.06522/26 (85%)

Example 25

[0449] The NOV25 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 25A. TABLE 25A NOV25 SequenceAnalysis SEQ ID NO: 61 379 bp NOV25a. TAATTAAATATGGGACAAGGTGTGCTGAAGAAGACTACTGGTCCTGTGAGATTGGCTG CG134005-01 DNASequence TATGTGAGAATCCACATGAGAGGCTAAGAATATTGTACACAAAGATCCTTGATGTTCTTGAGCAAATCCCTAAAAATGCAGCATATAAAAAGTGTACAGAACAGATTACAAATGAGAAGCTAGCTATGCTTAAAGTAGAACCAGATGTTAAAAAATTAGAAGACCAACTTCAAGATGGCCAAATAGAAGAGGTGATTCATCAGGCTGAAAATGAACTAAATGTGGTGAGAAAAACGATGCAGTGGAAACCATGGGGGGCAATAGTGGAAGAGCCTCCTGCCAATCAGTGAAAACAGCCAATATAATTATTAAATGACTTTG ORF Start: ATG at 10 ORF Stop: TGA at346 SEQ ID NO: 62 112 aa MW at 12827.8 kD NOV25a.MGQGVLKKTTGPVRLAVCENPHERLRILYTKILDVLEQIPKNAAYKKCTEQITNEKLA CG134005-01Protein Sequence MLKVEPDVKKLEDQLQDGQIEEVIHQAENELNVVRKTMQWKPWGAIVEEPPANQ

[0450] Further analysis of the NOV25a protein yielded the followingproperties shown in Table 25B. TABLE 25B Protein Sequence PropertiesNOV25a PSort 0.6500 probability located in cytoplasm: 0.1000 probabilityanalysis: located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen): 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0451] A search of the NOV25a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table25C. TABLE 25C Geneseq Results for NOV25a NOV25a Identities/ Residues/Similarities for Geneseq Protein/Organisim/Length[Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAG03840 Humansecreted protein, SEQ ID  4..112 86/109 (78%) 9e−44 NO: 7921—Homosapiens, 116 aa.  3..111 95/109 (86%) [EP1033401-A2, 06-SEP-2000]ABB62395 Drosophila melanogaster polypeptide  5..112 46/108 (42%) 5e−20SEQ ID NO 13977—Drosophila  4..111 68/108 (62%) melanogaster, 229 aa.[W0200171042-A2, 27-SEP-2001] AAG24556 Arabidopsis thaliana protein47..102 22/56 (39%) 6e−07 fragment SEQ ID NO: 28275—  6..61 36/56 (64%)Arabidopsis thaliana, 120 aa. [EP1033405-A2, 06-SEP-2000] AAG54944Arabidopsis thaliana protein 47..102 21/56 (37%) 3e−06 fragment SEQ IDNO: 70289—  6..61 35/56 (62%) Arabidopsis thaliana, 111 aa.[EP1033405-A2, 06-SEP-2000] AAG24557 Arabidopsis thaliana protein69..102 15/34 (44%) 0.002 fragment SEQ ID NO: 28276—  2..35 25/34 (73%)Arabidopsis thaliana, 94 aa. [EP1033405-A2, 06-SEP-2000]

[0452] In a BLAST search of public sequence datbases, the NOV25a proteinwas found to have homology, to the proteins shown in the BLASTP data inTable 25D. TABLE 25D Public BLASTP Results forNOV25a Identities/ NOV25aSimilarities Protein Residues/ for the Accession Match Matched ExpectNumber Protein/Organism/Length Residues Portion Value AAH20821 NADHdehydrogenase (ubiquinone) 1 4 . . . 112 86/109 (78%) 2e−43 alphasubcomplex. 5 (13 kD. B13) - 3 . . . 111 95/109 (86%) Homo sapiens(Human). 116 aa. Q16718 NADH-ubiquinone oxidoreductase 13 4 . . . 11286/109 (78%) 2e−43 kDa-B subunit (EC 1.6.5.3) (EC 2 . . . 110 95/109(86%) 1.6.99.3) (Complex 1-13Kd-B) (CI- 13Kd-B) (Complex 1 subunitB13) - Homo sapiens (Human). 115 aa. S28244 NADH dehydrogenase(ubiquinone) 4 . . . 112 84/109 (77%) 6e−43 (EC 1.6.5.3) complex 1 13K-Bchain - 3 . . . 111 96/109 (88%) bovine. 116 aa. P23935 NADH-ubiquinoneoxidoreductase 13 4 . . . 112 84/109 (77%) 6e−43 kDa-B subunit (EC1.6.5.3) (EC 2 . . . 110 96/109 (88%) 1.6.99.3) (Complex 1-13Kd-B) (CI-13Kd-B) (Complex 1 subunit B13) - Bos taurus (Bovine). 115 aa. Q9CY9010, 11 days embryo cDNA. RIKEN 4 . . . 112 76/109 (69%) 6e−39full-length enriched library. 3 . . . 111 90/109 (81%) clone:2810016H15.full insert sequence - Mus musculus (Mouse). 116 aa.

[0453] PFam analysis predicts that the NOV25a protein contains thedomains shown in the Table 25E. TABLE 25E Domain Analysis of NOV25a PfamNOV25a Identities/ Expect Domain Match Similarities Value Region for theMatched Region

Example 26

[0454] The NOV26 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 26A. TABLE 26A NOV26 SequenceAnalysis SEQ ID NO: 63 789 bp NOV26a. AGTGATGCAATGTCATCTTAATGGAGCGACTGAAAACTGATGTGTGTAGAATGAAA CG134014-01 DNASequence GAACACATGGAAGATAGAGTAAATGTGGCAGATTTCAGAAAACTAGAATGGCTTTTCCCAGAAACAACAGCAAATTTTGATAAACTGTTAATTCAATATCGGGGATTTTGTGCTTACACGTTTGCTGCAACAGATGGTCTTCTCCTTCCAGGTAATCCAGCAATTGGAATTTTAAAATATAAAGAAAAATATTACACATTCAATAGTAAAGATGCTGCATATTCATTTGCAGAAAATCCTGAACATTATATTGACATAGTTAGAGAAAAGGCCAAAAAAAATACAGAGTTAATTCAACTATTGGAACTTCATCAACAGTTTGAAACATTTATTCCATATTCTCAGATGAGAGATGCTGACAAACATTATATAAAACCAATTACAAAATGTGAAAGTAGCACACAGACGAATACACACATACTGCCACCAACGATTGTGAGATCATATGAGTGGAATGAATGGGAATTAAGAAGAAAAGCTATAAAATTGGCTAATTTGCGCCAGAAAGTTACTCACTCAGTACAAACTGATCTTAGTCACTTGAGAAGAGAAAATTGTTCCCAAGTGTACCCTCCAAAGGACACTAGCACCCAGTCCATGAGGGAAGACAGCACTGGGGTGCCCAGGCCTCAGATTTACTTGGCTGGTCTTCGTGGAGGAAAGAGCGAAATCACCGATGAGGTCAAGGTGAACTTAACTAGAGATGTGGATGAAACCTAA TTACAGACAAC ORF Start: ATG at 5 ORF Stop: TAAat 776 SEQ ID NO: 64 257 aa MW at 29869.6 kD NOV26a.MQCHLNGATVKTDVCRMKEHMEDRVNVADFRKLEWLFPETTANFDKLLIQYRGFCAYT CG134014-01Protein SequenceFAATDGLLLPGNPAIGILKYKEKYYTFNSKDAAYSFAENPEHYIDIVREKAKKNTELIQLLELHQQFETFIPYSQMRDADKHYIKPITKCESSTQTNTHILPPTIVRSYEWNEWELRRKAIKLANLRQKVTHSVQTDLSHLRRENCSQVYPPKDTSTQSMREDSTGVPRPQIYLAGLRGGKSEITDEVKVNLTRDVDET

[0455] Further analysis of the NOV26a protein yielded the followingproperties shown in Table 26B. TABLE 26B Protein Sequence PropertiesNOV26a PSort 0.4500 probability located in cytoplasm: 0.3000 probabilityanalysis: located in microbody (peroxisome): 0.1000 probability locatedin mitochondrial matrix space: 0.1000 probability located in lysosome(lumen) SignalP No Known Signal Sequence Predicted analysis:

[0456] A search of the NOV26a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table26C. TABLE 26C Geneseq Results for NOV26a NOV26a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value ABB68169Drosophila melanogaster polypeptide  39..208 50/176 (28%) 2e−08 SEQ IDNO 31299—Drosophila 404..570 79/176 (44%) melanogaster, 576 aa.[WO200171042-A2, 27-SEP-2001] AAB68357 Amino acid sequence of a maize117..229 32/115 (27%) 7.1 ZmMAD3 protein—Zea mays, 270 124..221 49/115(41%) aa. [WO200131017-A2, 03-MAY- 2001] AAG91801 C glutamicum proteinfragment SEQ  26..106 29/85 (34%) 7.1 ID NO: 5555—Corynebacterium137..213 40/85 (46%) glutamicum, 231 aa. [EP1108790- A2, 20-JUN-2001]ABG09185 Novel human diagnostic protein 133..194 18/63 (28%) 9.3#9176—Homo sapiens, 348 aa. 130..192 31/63 (48%) [WO200175067-A2,11-OCT-2001] AAB84880 Bacillus subtillis CodY—Bacillus  16..145 34/136(23%) 9.3 subtilis, 257 aa. [WO200129183-A2,  60..193 62/136 (45%)26-APR-2001]

[0457] In a BLAST search of public sequence datbases, the NOV26a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 26D. TABLE 26D Public BLASTP Results for NOV26a NOV26a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q95JU3Hypothetical 71.1 kDa protein -  1 . . . 257 252/257 (98%)  e−147 Macacafascicularis (Crab eating 366 . . . 622 253/257 (98%) macaque)(Cynomolgus monkey). 622 aa. Q9DAP6 1700003M02Rik protein - Mus  5 . . .257 199/253 (78%)  e−118 musculus (Mouse). 257 aa.  5 . . . 257 229/253(89%) Q95K32 Hypothetical 51.7 kDa protein -  1 . . . 114 110/114 (96%)4e−60 Macaca fascicularis (Crab eating 338 . . . 451 111/114 (96%)macaque) (Cynomolgus monkey). 452 aa. Q95JX1 Hypothetical 45.5 kDaprotein -  1 . . . 111 110/111 (99%) 5e−60 Macaca fascicularis (Crabeating 284 . . . 394 110/111 (99%) macaque) (Cynomolgus monkey). 397 aa.Q8T4E2 AT02388p - Drosophila  39 . . . 208  50/176 (28%) 5e−08melanogaster (Fruit fly). 576 aa. 404 . . . 570  79/176 (44%)

[0458] PFam analysis predicts that the NOV26a protein contains thedomains shown in the Table 26E. TABLE 26E Domain Analysis of NOV26a PfamNOV26a Identities/ Expect Domain Match Similarities Value Region for theMatched Region

Example 27

[0459] The NOV27 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 27A. TABLE 27A NOV27 SequenceAnalysis SEQ ID NO: 65 344 bp NOV27a. GTGATGATATGGCGACAACAAATTTTAATCTGCGACTTGAGCAAGATTTGCGTGATCG CG134023-01 DNASequence GGCATTTCCAGTGTTTGAGCGTTATGGACTGAGCGCATCACAAGCCTTTAAATTGTTTTTAACACAAGTTGCTGAGACCAATAAAATTCCCTTGTCTTTTGATTATGCAGAGACAGAGAATGTGCCGAATAGTGTCACAAGAAAAGCATTGACTGAAGCAAAAAATAGAACTGATTTTTCAGATGCTTATGAAACACCTGAAGAATTTATGAAAGCGATGCAAGAATTAGCC AATGCGTAAGATATTAGCTGAAAGCCAATTTAAGAGAGATATTAAAAAGCAATT ORF Start: ATG at 9 ORFStop: TAA at 297 SEQ ID NO: 66 96 aa MW at 11006.2 kD NOV27a,MATTNFNLRLEQDLRDRAFPVFERYGLSASQAFKLFLTQVAETNKIPLSFDYAETENV CG134023-01Protein Sequence PNSVTRKALTEAKNRTDFSDAYETPEEFMKAMQELANA

[0460] Further analysis of the NOV27a protein yielded the followingproperties shown in Table 27B. TABLE 27B Protein Sequence PropertiesNOV27a PSort 0.4500 probability located in cytoplasm; 0.4267 probabilityanalysis: located in mitochondrial matrix space: 0.1042 probabilitylocated in mitochondrial inner membrane: 0.1042 probability located inmitochondrial intermembrane space SignalP No Known Signal SequencePredicted analysis:

[0461] A search of the NOV27a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table27C. TABLE 27C Geneseq Results for NOV27a NOV27a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value ABP25789Streptococcus polypeptide SEQ ID  8..47 16/40 (40%) 0.12 NO754—Streptococcus agalactiae,  6..45 24/40 (60%) 97 aa. [WO200234771-A2,02-MAY- 2002] ABP25790 Streptococcus polypeptide SEQ ID  3..54 16/52(30%) 0.26 NO 756—Streptococcus pyogenes, 13..64 25/52 (47%) 104 aa.[WO200234771-A2, 02- MAY-2002] AAG84928 Shrimp white spot Bacilliformvirus 32..95 22/68 (32%) 1.0 (WSBV) protein 19—White spot 715..782 29/68(42%) syndrome virus, 783 aa. [WO200138351-A2, 31-MAY-2001] AAY97010 S.cerevisiae essential gene YJL010C 29..93 15/65 (23%) 5.1product—Saccharomyces cerevisiae, 202..265 30/65 (46%) 666 aa.[WO200039342-A2, 06-JUL- 2000] AAW89421 Moraxella catarrhalis VH1925..73 18/49 (36%) 6.7 lactoferrin binding protein 2 (Lbp2)— 566..61427/49 (54%) Moraxella catarrhalis, 905 aa. [WO9855606-A2, 10-DEC-1998]

[0462] In a BLAST search of public sequence datbases, the NOV27a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 27D. TABLE 27D Public BLASTP Results for NOV27a NOV27a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9REP3 Negativeregulator of translation -  1 . . . 92 65/92 (70%) 3e−28 Zymomonasmobilis. 93 aa.  1 . . . 89 75/92 (80%) Q9X443 Negative regulator oftranslation -  1 . . . 88 34/95 (35%) 3e−06 Haemophilus influenzae. 98aa.  1 . . . 91 50/95 (51%) P71357 Hypothetical protein HI0710 -  1 . .. 88 34/95 (35%) 1e−05 Haemophilus influenzae. 98 aa.  1 . . . 91 51/95(52%) Q8UGV0 Hypothetical protein Atu0935 -  9 . . . 71 20/63 (31%)0.011 Agrobacterium tumefaciens (strain 10 . . . 66 34/63 (53%) C58/ATCC33970). 91 aa. Q97SQ1 Hypothetical protein SP0275 -  1 . . . 91 22/91(24%) 0.018 Streptococcus pneumoniae. 87 aa.  1 . . . 86 47/91 (51%)

[0463] PFam analysis predicts that the NOV27a protein contains thedomains shown in the Table 27E. TABLE 27E Domain Analysis of NOV27a PfamNOV27a Identities/ Expect Domain Match Similarities Value Region for theMatched Region

Example 28

[0464] The NOV28 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 28A. TABLE 28A NOV28 SequenceAnalysis SEQ ID NO: 67 445 bp NOV28a. GATTAAATTTCCTCTATTGCTTGGTATGGTGCTGTTCTGGGAACAGACAAAATCACTT CG134032-01 DNA SequenceCACTGTCTTCAAGTACAACAGGACTTCAGCCAGAGCCGCACCATCCCCAGCCGCACCGTGGCCATCAGCGACGCTGCACAGTTACCTCATGACTACTGCACCACACAGGGGGGCACTCTTCTCACCACACGGGGAGGAACTCAAATCTTTTATGATAGAAAGTTTCTGTTGGATTATTGCAATTCTCCCATGGTTCAGACCCCACCCTGCCATCTACCAAATATCCCAGAAGTCACTAGCCCTGGCACCTTAATCGAAGACTCCAGAGTAGAAGTAAACAATTTGAACAACATAAACAATCATGAGAGGAAACACGCAGTTGGGGATGATGCTCAGTTTGAGATGGGC ATCTGACTCTCCTGCAAGGATTAGAAGAAAAGCAGCAAT ORF Start: ATG at 26 ORF Stop: TGA at410 SEQ ID NO: 68 128 aa MW at 14404.0 kD NOV28a,MVLFWEQTKSLHCLQVQQDFSQSRTIPSRTVAISDAAQLPHDYCTTQGGTLLTTRGGT CG134032-01Protein sequenceQIFYDRKFLLDYCNSPMVQTPPCHLPNIPEVTSPGTLIEDSRVEVNNLNNINNHERKH AVGDDAQFEMGI

[0465] Further analysis of the NOV28a protein yielded the followingproperties shown in Table 28B. TABLE 28B Protein Sequence PropertiesNOV28a PSort 0.6500 probability located in cytoplasm; 0.2379 probabilityanalysis: located in lysosome (lumen): 0.1000 probability located inmitochondrial matrix space: 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0466] A search of the NOV28a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table28C. TABLE 28C Geneseq Results for NOV28a NOV28a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value+HZ,49 AAY96148Human elF-4E binding protein 4E- 21..128 93/109 (85%) 6e−49 BP2—Homosapiens, 120 aa. 12..120 98/109 (89%) [US6111077-A, 29-AUG-2000]AAW94275 Human elF-4E-binding protein 4E- 21..128 93/109 (85%) 6e−49BP2—Homo sapiens, 120 aa. 12..120 98/109 (89%) [US5874231-A,93-FEB-1999] ABB57347 Mouse ischaemic condition related 23..128 54/108(50%) 1e−19 protein sequence SEQ ID NO:973— 12..117 72/108 (66%) Musmusculus, 117 aa. [WO200188188-A2, 22-NOV-2001] ABB97146 Human tumourantigen related 23..128 55/109 (50%) 3e−19 protein SEQ ID NO 48—Homo12..118 72/109 (65%) sapiens, 118 aa. [WO200210369-A1, 07-FEB-2002]AAY96147 Human elF-4E binding protein 4E- 23..128 55/109 (50%) 3e−19BP1—Homo sapiens, 118 aa. 12..118 72/109 (65%) [US6111077-A,29-AUG-2000]

[0467] In a BLAST search of public sequence datbases, the NOV28a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 28D. TABLE 28D Public BLASTP Results for NOV28qa NOV28aIdentities/ Protein Residues/ Similarities for Accession Match theMatched Expect Number Protein/Organism/Length Residues Portion ValueQ13542 4E-binding protein 2 (Eukaryotic 21 . . . 128 93/109 (85%) 1e−48translation initiation factor 4E binding 12 . . . 120 98/109 (89%)protein 2) - Homo sapiens (Human). 120 aa. P70445 PHAS-II (Eukaryotictranslation 21 . . . 128 90/109 (82%) 1e−46 initiation factor 4E bindingprotein 2) - 12 . . . 120 96/109 (87%) Mus musculus (Mouse), 120 aa.Q9CZ40 Eukaryotic translation initiation factor 23 . . . 128 55/108(50%) 8e−20 4E binding protein 1 - Mus musculus 12 . . . 117 72/108(65%) (Mouse). 117 aa. Q62622 PHAS-I - Rattus norvegicus (Rat). 23 . . .128 54/108 (50%) 1e−19 117 aa. 12 . . . 117 73/108 (67%) Q60876Eukaryotic translation initiation factor 23 . . . 128 54/108 (50%) 3e−194E binding protein 1 (Insulin- 12 . . . 117 72/108 (66%) stimulatedEIF-4E binding protein PHAS-I) - Mus musculus (Mouse). 117 aa.

[0468] PFam analysis predicts that the NOV28a protein contains thedomains shown in the Table 28E TABLE 28E Domain Analysis of NOV28a PfamNOV28a Identities/ Expect Domain Match Similarities Value Region for theMatched Region

Example 29

[0469] The NOV29 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 29A. TABLE 29A NOV29 SequenceAnalysis SEQ ID NO: 69 552 bp NOV29a. TCCAGGCAACGCTGCGGCTCCGCCCACGTCATGGCGCCCGAGGAGAACGCGGGGACAG CG134304-01 DNA SequenceAACTCTGGCTGCAGGGTTTCGAGCGCCGCTTCCTGGCGGCGCGCTCACTGCGCTCCTTCCCCTGGCAGAGCTTAGAGGCAAAGTTAAGAGACTCATCAGATTCTGAGCTGCTGCGGGATATTTTGCAGAAGACGAGGGCTGTCCACACGGAGCCTTTGGACGAGCTGTACGAGGTGCTGGCGGAGACTCTGATGGCCAAGGAGTCCACCCAGGGCCACCGGAGCTATTTGCTGACGTGCTGTATTGCCCAGAAGCCATCGTGTCACTGGTCGGGGTCCTGCGGAGGCTGGCTGCCTGCCGGGAGCACAAGCAGGCTCCTGAGGTCTACCTGGCCTTTACCGTCCGCAACCCAGAGACGTGCCAGCTGTTCACCACCGAGCCAGGCTGGACTGGGATCAGATGGGAAGTGGAAGCTCATCATGACCAGAAACTGTTTCCCTACAGAGAGCACTTGGAGATGGCAA TGCTGAACCTCACACTGTAGGACTCACACA ORF Start: ATG at 31 ORF Stop: TGA at 526 SEQID NO: 70 165 aa MW at 18617.9 kD NOV29a,MAPEENAGTELWLQGFERRFLAARSLRSFPWQSLEAKLRDSSDSELLRDILQKTRAVH CG134304-01Protein SequenceTEPLDELYEVLAETLMAKESTQGHRSYLLTCCIAQKPSCHWSGSCGGWLPAGSTSRLLRSTWPLPSATQRRASCSPPSQAGLGSDGKWKLIMTRNCFPTESTWRWQC

[0470] Further analysis of the NOV29a protein yielded the followingproperties shown in Table 29B. TABLE 29B Protein Sequence PropertiesNOV29a PSort 0.6279 probability located in microbody (peroxisome);0.1000 analysis: probability located in mitochondrial matrix space;0.1000 probability located in lysosome (lumen); 0.0000 probabilitylocated in endoplasmic reticulum (membrane) SignalP No Known SignalSequence Predicted analysis:

[0471] A search of the NOV29a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table29C. TABLE 29C Genesec1 Results for NOV29a NOV29a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAB93042 Humanprotein sequence SEQ ID  1..164 150/164 (91%) 4e−85 NO:11827—Homosapiens, 165 aa.  1..164 154/164 (93%) [EP1074617-A2, 07-FEB-2001]AAB36613 Human FLEXHT-35 protein  1..87  81/114 (71%) 6e−35 sequence SEQID NO:35—Homo  1..114  82/114 (71%) sapiens, 330 aa. [WO200070047- A2,23-NOV-2000] ABG13115 Novel human diagnostic protein  1..87  79/114(69%) 6e−34 #13106—Homo sapiens, 425 aa. 23..136  81/114 (70%)[WO200175067-A2, 11-OCT-2001] ABG13115 Novel human diagnostic protein 1..87  79/114 (69%) 6e−34 #13106—Homo sapiens, 425 aa. 23..136  81/114(70%) [WO200175067-A2, 11-OCT-2001] ABG09575 Novel human diagnosticprotein 19..97  60/79 (75%) 2e−22 #9566—Homo sapiens, 379 aa. 89..158 62/79 (77%) [WO200175067-A2, 11-OCT-2001]

[0472] In a BLAST search of public sequence datbases, the NOV29a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 29D. TABLE 29D Public BLASTP Results for NOV29a NOV29a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9NVL1 CDNAFLJ10661 fis. clone  1 . . . 164 150/164 (91%)  1e−84 NT2RP2006106 -Homo sapiens  1 . . . 164 154/164 (93%)  (Human). 165 aa. Q96G04 Similarto RIKEN cDNA  1 . . . 87  81/114 (71%) 2e−34 5730409G15 gene - Homo  1. . . 114 82/114 (71%) sapiens (Human). 330 aa. Q9CS89 5730409G15Rikprotein - Mus  1 . . . 87  62/114 (54%) 7e−22 musculus (Mouse). 319 aa 1 . . . 114 68/114 (59%) (fragment). Q96S85 Hypothetical 33.0 kDaprotein -  1 . . . 54   50/54 (92%) 1e−20 Homo sapiens (Human). 296 aa. 1 . . . 54   51/54 (93%) QSX0Q4 Hypothetical 45.6 kDa protein - 114 . .. 163  18/52 (34%) 1.5 Neurospora crassa. 420 aa.  36 . . . 87   26/52(49%)

[0473] PFam analysis predicts that the NOV29a protein contains thedomains shown in the Table 29E. TABLE 29E Domain Analysis of NOV29a PfamNOV29a Identities/ Expect Domain Match Similarities Value Region for theMatched Region

Example 30

[0474] The NOV30 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 30A. TABLE 30A NOV30 SequenceAnalysis SEQ ID NO:71 1411 bp NOV30a. TTCTGATCATGTCACTGGCAAGGCAATGCTTACCTCACTTGGCCTGAAGTTGGGGGAT CG134421-01 DNA SequenceCGTGTTGTTATTGCAGGACAGAAGGTTGGTACATTAAGATTTTGTGGAACAACTGAATTTGCAAGTGGGCAGTGGGCTGGCATTGAACTGGATGAACCAGAAGGAAAAAATAATGGAAGTCTTCCAAAAGTCCAGTACTTTAAATGTGCCCCCAAGTATGGTATTTTTGCACCTCTTTCAAACATAAGTAAAGCAAAACCTCGAAGCAAGAATATAACACACACTCCTTCTACAAAACCTCCTGTACCTCTCATCAGCTCCCAGAAAATTGACCTACCTCATCTCACCTCAAAACTAAATACTGGATTAATCACATCAAAAAAAGATACTGCTTCTCAGTCAACACTTTCATTGCCTCCTGGTCAACAACTTAAAACTCTGACACACAAAGATCTTGCCCTCCTTCGATCTCTCACCACCTCCTCCTCTACATCTTCTTTGCAACACAGACACACCTACCCCAAGAAACAGAATGCAATCAGCAGTAACAAGAAGACAATGACCAAAACCCCTTCCCTTTCATCCACAGCCAGTGCTGGTTTGAATTCCTCACCAACATCTACAGCAAATAATAGCCCTTGCCAGGCCGAACTCCGCCTCGGCAGACAGACTGTTACTCGTAGGACAGACACTCGCCA CCATTAGGTTCTTTGGGACAACAAACTTCGCTCCAGGATATTGGTATGGTATAGACCTTGAAAAACCCCATCCCAAGAATGATGGTTCAGTTCCACGTGTGCAGTATTTTAGCTCTTCTCCAAGATATGCAATATTTGCTCCCCCATCCAGCCTGCAAAOAGTAACAGATTCCCTGCATACCCTTTCAGAAATTTCTTCAAATAAACAGAACCATTCTTATCCTCCTTTTAGCACAAGTTTTAGCACAACTTCTGCTTCTTCCCAAAACGACATTAACACAACAAATCCTTTTTCCAAATCCAAACCTGCTTTGCCTCGCAGTTCGAGCAGCACCCCCACCGCACGTCGCATTCAACGCACCGTCAACCTCCACCAGGCGTCTCAGGTCCTCCTCACCAGCTCCAATGACATCCCTACTCTTAGCTATCTGGCCCCCACTGACTTTGCTTCAGGTATCTCCCTTGCACTTCAGCTCCCAAGCCCCAAGCCAAAAAATCATGCGTCAGTGGGTGACAACCGCTATTTCACCTCTAAGCCGAACCATGGAGTCTTAGTTCCACCGAGCAGACTGACCTATCCGGGAATTAATGCCTCAAAACTTCTGGATGACAATTCTTAAGCTTCTAAAATATTAAATAACCTCAAATATATATATTTGCTGTAAATAAAGAGTCCATCCTAAATGGTTTACTTTATTTAGCCATATTAAAATTT ORF Start: ATG at 26 ORF Stop: TAG at 701 SEQ ID NO:72 225 aa MW at 23826.7 kD NOV30a.MLTSLCLKLCDRVVTACQKVCTLRFCCTTEFASGQWAGIELDEPEGKNNCSVGKVQYP CG134421-01Protein SequenceKCAPKYCTFAPLSKISKAKCRRKNTTHTPSTKAACPLIRSQKIDVAHVTSKVNTCLMTSKKDSASESTLSLPPCEELKTVTEKDVALLCSVSSCSSTSSLEHRQSYPKKQNAISSNKKTMSKSPSLSSRASAGLNSSATSTANNSRCECELPLCRESVSCRTETGHH

[0475] Further analysis of the NOV30a protein yielded the followingproperties shown in Table 30B. TABLE 30B Protein Sequence PropertiesNOV30a PSort 0.6500 probability located in cytoplasm: 0.1000 probabilityanalysis: located in mitochondrial matrix space: 0.1000 probabilitylocated in lysosome (lumen): 0.0000 probability located in endo-plasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0476] A search of the NOV30a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table30C. TABLE 30C Geneseq Results for NOV30a NOV30a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAY93488 Aminoacid sequence of a potassium   1..153 76/153 (49%) 4e−33 channelinteractor polypeptide— 108..252 97/153 (62%) Rattus sp. 267 aa.[WO200031133- A2, 02-JUN-2000] ABB97353 Novel human protein SEQ ID NO:  1..147 75/147 (51%) 5e−32 621—Homo sapiens, 547 aa. 288..426 95/147(64%) [WO200222660-A2, 21-MAR-2002] AAU74342 Humancytoskeleton-associated   1..147 75/147 (51%) 5e−32 protein (CYSKP)#13—Homo 288..426 95/147 (64%) sapiens, 547 aa. [WO200185942-A2,15-NOV-2001] ABG29271 Novel human diagnostic protein   1..64 64/64(100%) 1e−31 #29262—Homo sapiens, 574 aa. 293..356 64/64 (100%)[WO200175067-A2, 11-OCT-2001] ABG29271 Novel human diagnostic protein  1..64 64/64 (100%) 1e−31 #29262—Homo sapiens, 574 aa. 293..356 64/64(100%) [WO200175067-A2, 11-OCT-2001]

[0477] In a BLAST search of public sequence datbases, the NOV30a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 30D. TABLE 30D Public BLASTP Results for NOV30a NOV30a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q96BR7Hypothetical 53.2 kDa protein -  1 . . . 212  212/212 (100%) e−116 Homosapiens (Human). 494 aa. 170 . . . 381  212/212 (100%) Q9H7C0 CDNA:FLJ21069 fis, clone  1 . . . 212 211/212 (99%) e−115 CAS01594 - Homosapiens 170 . . . 381 211/212 (99%) (Human). 492 aa. Q96MA5 CDNAFLJ32705 fis. clone  1 . . . 192  44/192 (99%) e−104 TESTI2000600.weakly similar to 127 . . . 318 192/192 (99%) restin - Homo sapiens(Human). 345 aa. Q9D2L0 4833417L20Rik protein - Mus  1 . . . 212 167/212(78%) 5e−88 musculus (Mouse). 694 aa. 277 . . . 487 180/212 (84%) Q9D3G05830409B12Rik protein - Mus  1 . . . 212 167/212 (78%) 5e−88 musculus(Mouse). 488 aa.  61 . . . 271 180/212 (84%)

[0478] PFam analysis predicts that the NOV30a protein contains thedomains shown in the Table 30E. TABLE 30E Domain Analysis of NOV30aIdentities/ NOV30a Similarities Pfam Match for the Matched Expect DomainRegion Region Value CAP_GLY 27. . . 69 27/43 (63%) 6.1e−22 38/43 (88%)

Example 31

[0479] The NOV31 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 31A. TABLE 31A NOV31 SequenceAnalysis SEQ ID NO: 73 3974 bp NOV31a.GGTTCCTGAGCACTTACTTGCACACAGATTCAATGATGGAGGTATCAGCCCCACCATA CG134895 DNASequence GGAAGCTGAAATAGTAGTTTCCTTCATATTTCTGGACAGCCCCTCTGTGGGTGCAACAACATTCCCTGACAAAGGTGCAGCCTCCATATGAAATCTGATCTTGGTCTGAGACAATGTCTTCTGCCCAGTTTCACTGGATGACTCTTGTCCCCTTTTTGTCCTGCCCCCTATCCAGGTCGTTTTCTGATGTGACGGCTGAGAC ATGAGATCTTCAGCCTCCAGGCTCTCCAGTTTTTCGTCGAGAGATTCACTATGGAATCGGATGCCGGACCAGATCTCTGTCTCGGAGTTCATCGCCGAGACCACCGAGGACTACAACTCGCCCACCACGTCCAGCTTCACCACGCGGCTGCACAACTGCAGGAACACCGTCACGCTGCTGGAGGAGGCTCTAGGCCAAGATAGAACAGCCCTTCAGAAAGTGAAGAAGTCTGTAAAAGCAATATATAATTCTGGTCAAGATCATGTACAAAATGAAGAAAACTATGCACAAGTTCTTGATAAGTTTGGGAGTAATTTTTTAAGTCGAGACAACCCCGACCTTGGCACCGCGTTTGTCAAGTTTTCTACTCTTACAAAGGAACTGTCCACACTGCTGAAAAATCTGCTCCAGGGTTTGAGCCACAATGTGATCTTCACCTTGGATTCTTTGTTAAAAGGAGACCTAAAGGGAGTCAAAGGAGATCTCAAGAAGCCATTTGACAAAGCCTGGAAAGATTATGAGACAAAGTTTACAAAAATTGAGAAAGAGAAAAGAGAGCACGCAAAACAACATGGGATGATCCGCACAGAGATAACAGGAGCTGAGATTGCGGAAGAAATGGAGAAGGAAAGGCGCCTCTTTCAGCTCCAAATGTGTGAATATCTCATTAAAGTTAATGAAATCAAGACCAAAAAGGGTGTGGATCTGCTGCAGAATCTTATAAAGTATTACCATGCACAGTGCAATTTCTTTCAAGATGGCTTGAAAACAGCTGATAAGTTGAAACAGTACATTGAAAAACTGGCTGCTGATTTATATAATATAAAACAGACCCAGGATGAAGAAAAGAAACAGCTAACTGCACTCCGAGACTTAATAAAATCCTCTCTTCAACTGGATCAGAAAGAATCTAGGAGAGATTCTCAGAGCCGGCAAGGAGGATACAGCATGCATCAGCTCCAGGGCAATAAGGAATATGGCAGTGAAAAGAAGGGGTACCTGCTAAAGAAAAGTGACGGGATCCGGAAAGTATGGCAGAGGAGGAAGTGTTCAGTCAAGAATGGGATTCTGACCATCTCACATGCCACATCTAACAGGCAACCAGCCAAGTTGAACCTTCTCACCTGCCAAGTAAAACCTAATGCCGAAGACAAAAAATCTTTTGACCTGATATCACATAATAGAACATATCACTTTCAGGCAGAAGATGAGCAGGATTATGTAGCATGGATATCAGTATTGACAAATAGCAAAGAAGAGGCCCTAACCATGGCCTTCCGTGGAGAGCAGAGTGCGGGAGAGAACAGCCTGGAAGACCTGACAAAAGCCATTATTGAGGATGTCCAGCGGCTCCCAGGGAATGACATTTGCTGCGATTGTGGCTCATCAGAACCCACCTGGCTTTCAACCAACTTGGGTATTTTGACCTGTATAGAATGTTCTGGCATCCATAGGGAAATGGGGGTTCATATTTCTCGCATTCAGTCTTTGGAACTAGACAAATTAGGAACTTCTGAACTCTTGCTGGCCAAGAATGTAGGAAACAATAGTTTTAATGATATTATGGAAGCAAATTTACCCAGCCCCTCACCAAAACCCACCCCTTCAAGTGATATGACTGTACGAAAAGAATATATCACTGCAAAGTATGTAGATCATAGGTTTTCAAGGAAGACCTGTTCAACTTCATCAGCTAAACTAAATGAATTGCTTGAGGCCATCAAATCCAGGGATTTACTTGCACTAATTCAAGTCTATGCAGAAGGGGTAGAGCTAATGGAACCACTGCTGGAACCTGGGCAGGAGCTTGGGGAGACAGCCCTTCACCTTGCCGTCCGAACTGCAGATCAGACATCTCTCCATTTGGTTGACTTCCTTGTACAAAACTGTGGGAACCTGGATAAGCAGACGGCCCTGGGAAACACAGTTCTACACTACTGTAGTATGTACAGTAAACCTGAGTGTTTGAAGCTTTTGCTCAGGAGCAAGCCCACTGTGGATATAGTTAACCAGGCTGGAGAAACTGCCCTAGACATAGCAAAGAGACTAAAAGCTACCCAGTGTGAAGATCTGCTTTCCCAGGCTAAATCTGGAAAGTTCAATCCACACGTCCACGTAGAATATGAGTGGAATCTTCGACAGGAGGAGATAGATGAGAGCGATGATGATCTGGATGACAAACCAAGCCCTATCAAGAAAGAGCGCTCACCCAGACCTCAGAGCTTCTGCCACTCCTCCAGCATCTCCCCCCAGGACAAGCTGGCACTGCCAGGATTCAGCACTCCAAGGGACAAACAGCGGCTCTCCTATGGAGCCTTCACCAACCAGATCTTCGTTTCCACAAGCACAGACTCGCCCACATCACCAACCACGGAGGCTCCCCCTCTGCCCCCTAGGAACGCCGGGAAAGGTCCAACTGGCCCACCTTCAACACTCCCTCTAAGCACCCAGACCTCTAGTGGCAGCTCCACCCTATCCAAGAAGAGGCCTCCTCCCCCACCACCCGGACACAAGAGAACCCTATCCGACCCTCCCAGCCCACTACCTCATGGGCCCCCAAACAAAGGCGCAGTTCCTTGGGGTAACGATGGGGGTCCATCCTCTTCAAGTAAGACTACAAACAAGTTTGAGGGACTATCCCAGCAGTCGAGCACCAGTTCTGCAAAGACTGCCCTTGGCCCAAGAGTTCTTCCTAAACTACCTCAGAAAGTGGCACTAAGGAAAACAGATCATCTCTCCCTAGACAAAGCCACCATCCCGCCCGAAATCTTTCAGAAATCATCACAGTTGGCAGAGTTGCCACAAAAGCCACCACCTGGAGACCTGCCCCCAAAGCCCACAGAACTGGCCCCCAAGCCCCAAATTGGAGATTTGCCGCCTAGGCCAGGAGAACTGCCCCCCAAACCACAGCTGGGGGACCTGCCACCCAAACCCCAACTCTCAGACTTACCTCCCAAACCACAGATGAAGGACCTGCCCCCCAAACCACAGCTGGGAGACCTGCTAGCAAAATCCCAGACTGGAGATGTCTCACCCAAGGCTCAGCAACCCTCTGAGGTCACACTGAAGTCACACCCATTGGATCTATCCCCAAATGTGCAGTCCAGAGACGCCATCCAAAAGCAAGCATCTGAAGACTCCAACGACCTCACGCCTACTCTGCCAGAGACGCCCGTACCACTGCCCAGAAAAATCAATACGGGGAAAAATAAAGTGAGGCGAGTGAAGACCATTTATGACTGCCAGGCAGACAACGATGACGAGCTCACATTCATCGAGGGAGAAGTGATTATCGTCACAGGGGAAGAGGACCAGGAGTGGTGGATTGGCCACATCGAAGGACAGCCTGAAAGGAAGGGGGTCTTTCCAGTGTCCTTTGTTCATATCCTGTCTG ACTAGCAAAACGCAGAACCTTAAGATTGTCCACATCCTTCATGCAAGACTGCTGCCTTCATGTAACCCTGGGCACAGTGTGTATATAGCTGCTGTTACAGAGTAAGAAACTCATGGAAGGGCCACCTCAGGAGGGGGATATAATGTGTGTTGTAAATATCCTGTGGTTTTCTGCCTTCACCAGTATGAGGGTAGCCTCGGACCCGGCGCGCCTTACTGGTTTGCCAAAGCCATCCTTGGCATCTAGCACTTACATCTCTCTATGCTGTTCTACAAGCAAACAAACAAAAATAGGAGTATAGGAACTGCTGGCTTTGCAAA ORF Start: ATG at 261 ORF Stop: TAG at3657 SEQ ID NO: 74 1132 aa MW at 125838.0 kD NOV31a.MRSSASRLSSFSSRDSLWNRMPDQISVSEFIAETTEDYNSPTTSSFTTRLHNCRNTVT CG134895-01Protein SequenceLLEEALGQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKLAADLYNIKQTQDEEKKQLTALRDLIKSSLQLDQKESRRDSQSRQGGYSMHQLQGNKEYGSEKKGYLLKKSDGIRKVWQRRKCSVKNGILTISHATSNRQPAKLNLLTCQVKPNAEDKKSFDLISHNRTYHFQAEDEQDYVAWISVLTNSKEEALTMAFRGEQSAGENSLEDLTKAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEANLPSPSPKPTPSSDMTVRKEYITAKYVDHRFSRKTCSTSSAKLNELLEAIKSRDLLALIQVYAEGVELMEPLLEPGQELGETALHLAVRTADQTSLHLVDFLVQNCGNLDKQTALGNTVLHYCSMYSKPECLKLLLRSKPTVDIVNQAGETALDIAKRLKATQCEDLLSQAKSGKFNPHVHVEYEWNLRQEEIDESDDDLDDKPSPIKKERSPRPQSFCHSSSISPQDKLALPGFSTPRDKQRLSYGAFTNQIFVSTSTDSPTSPTTEAPPLPPRNAGKGPTGPPSTLPLSTQTSSGSSTLSKKRPPPPPPGHKRTLSDPPSPLPHGPPNKGAVPWGNDGGPSSSSKTTNKFEGLSQQSSTSSAKTALGPRVLPKLPQKVALRKTDHLSLDKATIPPEIFQKSSQLAELPQKPPPGDLPPKPTELAPKPQIGDLPPKPGELPPKPQLGDLPPKPQLSDLPPKPQMKDLPPKPQLGDLLAKSQTGDVSPKAQQPSEVTLKSHPLDLSPNVQSRDAIQKQASEDSNDLTPTLPETPVPLPRKINTGKNKVRRVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHILSD

[0480] Further analysis of the NOV31a protein yielded the followingproperties shown in Table 31B. TABLE 31B Protein Sequence PropertiesNOV31a PSort 0.9200 probability located in mitochondrial matrix space:analysis: 0.7466 probability located in nucleus; 0.6000 probabilitylocated in mitochondrial inner membrane: 0.6000 probability located inmitochondrial intermembrane space SignalP No Known Signal SequencePredicted analysis:

[0481] A search of the NOV31a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table31C. TABLE 31C Geneseq Results for NOV31a NOV31a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAW77286 Bovinedifferentiation enhancing   1..1132 1088/1135 (95%) 0.0 factor 1protein—Bos sp. 1129 aa.   1..1129 1106/1135 (96%) [WO9836065-A1,20-AUG-1998] AAM40068 Human polypeptide SEQ ID NO 193..1132  939/940(99%) 0.0 3213—Homo sapiens, 940 aa.   1..940  939/940 (99%)[WO200153312-A1, 26-JUL- 2001] AAW77287 Zebrafish differentiation  1..1132  879/1162 (75%) 0.0 enhancing factor 1 protein—   1..1151 981/1162 (83%) Brachydanio rerio, 1151 aa. [WO9836065-A1, 20-AUG-1998]AAW77290 Human differentiation enhancing  21..1132  619/1120 (55%) 0.0factor 2 gene—Homo sapiens,   1..1006  746/1120 (66%) 1006 aa.[WO9836065-A1, 20- AUG-1998] AAW77288 Zebrafish differentiation  21..853 540/842 (64%) 0.0 enhancing factor 2 protein—   1..826  650/842 (77%)Brachydanio rerio, 982 aa. [WO9836065-A1, 20-AUG-1998]

[0482] In a BLAST search of public sequence datbases, the NOV31a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 31D. TABLE 31D Public BLASTP Results for NOV31a NOV31a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9QWY8ADP-ribosylation factor-directed 1 . . . 1132 1091/1147 (95%) 0.0 GTPaseactivating protein isoform 1 . . . 1147 1109/1147 (96%) a - Mus musculus(Mouse). 1147 aa. O97902 Differentiation enhancing factor I - 1 . . .1132 1089/1135 (95%) 0.0 Bos taurus (Bovine). 1129 aa. 1 . . . 11291107/1135 (96%) Q9Z2B6 ADP-ribosylation factor-directed 1 . . . 11321020/1147 (88%) 0.0 GTPase activating protein isoform 1 . . . 10901045/1147 (90%) b - Mus musculus (Mouse). 1090 aa. Q9ULH1 KIAA1249protein - Homo 184 . . . 1132    949/949 (100%) 0.0 sapiens (Human). 949aa 1 . . . 949    949/949 (100%) (fragment). O43150 KIAA0400 protein -Homo 21 . . . 1132   619/1120 (55%) 0.0 sapiens (Human). 1006 aa. 1 . .. 1006  746/1120 (66%)

[0483] PFam analysis predicts that the NOV31a protein contains thedomains shown in the Table 31E. TABLE 31E Domain Analysis of NOV31aIdentities/ Similarities NOV31a for the Pfam Match Matched Expect DomainRegion Region Value PH 328 . . . 419 25/92 (27%) 2.8e−15 67/92 (73%)ArfGap 442 . . . 565 51/139 (37%)  1.4e−35 95/139 (68%)  ank 603 . . .638 10/36 (28%) 0.0045  28/36 (78%) ank 639 . . . 671 10/33 (30%)0.00026 24/33 (73%) SH3 1073 . . . 1130 20/61 (33%) 4.7e−10 43/61 (70%)

Example 32

[0484] The NOV32 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 32A. TABLE 32A NOV32 SequenceAnalysis SEQ ID NO:75 1739 bp NOV32a, ACCTGGCCCTACCTAAGCATGATCATGGAAAGCAAGTTCCGGGAGAAACTTGAGCCCA CG134922-01 DNA SequenceAGATCCGAGAGAAGAGCATCCACCTGAGCACCTTTACCTTTACCAAGCTCTACTTTGGACAGAAGTCTCCCAGGGTCAACGGTGTCAAGGCACACACTAATACGTGCAACCGAAGACGTCTGACTGTGGACCTGCAGATCTGCCCCAGCACCACCTGGGATGTAAGCAGTGGGGGCTGCTTCTGTGTCCCCATGAAAGACACCTGGGCAGAGATGGGACAGGGGGACAGCAGGGGTGGAAAAGTGGGCAGCGTGTTTACCAAGAGCCCCTCCTTTTCATCTTCAGGGTATCGTGGGGTGAGCTACATCGGGGACTGTTATATCAGTGTGGAGCTGCAGAAGATTCATGCTGGTGTGAACGGGATCCAGGTGGGTGGAGCCCGGCGGGTCATCCTGGAGCCCCTCCTATTGGACAAGCCCTTTGTGGGAGCCGTGACTGTGTTCTTCCTTCAGAAGCCGCCTAATAGCTTCCCTCTGCCCCTGAAGCACCTACAGATCAACTGGACTGGCCTGACCAACCTGCTGGATGCGCCGGGAATCAATGATGTGTCAGACAGCTTACTGGAGGACCTCATTGCCACCCACCTCGTGCTGCCCAACCGTGTGACTGTGCCTGTGAAGAAGGGGCTGGATCTGACCAACCTGCGCTTCCCTCTGCCCTGTGGGGTGATCAGAGTGCACTTGCTGGAGGCAGAGCAGCTGGCCCAGAAGGACAACTTTCTGGGGCTCCGAGGCAAGTCAGATCCCTACGCCAAGGTGAGCATCGGCCTACAGCATTTCCGGAGTAGGACCATCTACAGGAACCTGAACCCCACCTGGAACGAAGTGTTCCAGTTCATGGTGTACGAAGTCCCTGGACAGGACCTGGAGGTAGACCTGTATGATGAGGATACCGACAGGGATGACTTCCTGGGCAGCCTGCAGATCTGCCTTGGAGATGTCATGACCAACAGAGTGGTGGATGAGTGGTTTGTCCTGAATGACACAACCAGCGGGCGGCTGCACCTGCGGCTGGAGTGGCTTTCATTGCTTACTGACCAAGACGTTCTGACTGAGGACCATGGTGGCCTTTCCACTGCCATTCTCGTGGTCTTCTTGGAGAGTGCCTGCAACTTGCCGAGAAACCCTTTTGACTACCTGAATCGTGAATATCGAGCCAAAAAACTCTCCAGGTTTGCCAGAAACAAGGTCAGCAAAGACCCTTCTTCCTATGTCAAACTATCTGTAGGCAAGAAGACACATACAAGTAAGACCTGTCCCCACAACAAGGACCCTGTGTGGAGCCAGGTGTTCTCCTTCTTTGTGCACAATGTGGCCACTGAGCGGCTCCATCTGAAGGTGCTTGATGATGACCAGGAGTGTGCTCTGGGAATGCTGGAGGTCCCCCTGTGCCAGATCCTCCCCTATGCTGACCTCACTCTTGAGCAGCGCTTTCAGCTGGACCACTCAGGCCTGGACAGCCTCATCTCCATGAGGCTGGTGCTTCGGGTAAACCTAACACCATGTACCAGCAGTGGAGCTGATCCCTACGTCCGTGTCTACTTGTTGCCACAAAGGAAGTGGGCATGTCGTAAGAAGACTTCAGTGAAGCGGAAGACCTTGGAACCCCTGTTTGATGAGACGTAAGTGGGCTGGTGGCCTGCCTAGAGTGCCTCACCCATTCAAGTATTTTCCAAGTACCT ORF Start: ATGat 19 ORF Stop: TAA at 1681 SEQ ID NO: 76 554 aa MW at 62597.4 kDNOV32a, MIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDLCG134922-01 Protein SequenceQICPSSTWDVSSGGCFCVPMKDTWAEMGQGDSRGGKVGSVFTKSPSFSSSGYRCVSYIGDCYISVELQKIHAGVNGIQVGGARRVILEPLLLDKPFVGAVTVFFLQKPPNSFPLPLKHLQINWTGLTNLLDAPGINDVSDSLLEDLIATHLVLPNRVTVPVKKGLDLTNLRFPLPCGVIRVHLLEAEQLAQKDNFLGLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFQFMVYEVPGQDLEVDLYDEDTDRDDFLGSLQICLGDVMTNRVVDEWFVLNDTTSGRLHLRLEWLSLLTDQDVLTEDHGGLSTAILVVFLESACNLPRNPFDYLNGEYRAKKLSRFARNKVSKDPSSYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDDQECALGMLEVPLCQILPYADLTLEQRFQLDHSGLDSLISMRLVLRVNLTPCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDET

[0485] Further analysis of the NOV32a protein yielded the followingproperties shown in Table 32B. TABLE 32B Protein Sequence PropertiesNOV32a PSort 0.4500 probability located in cytoplasm: 0.1523 analysis:probability located in microbody (peroxisome): 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probability located inlysosome (lumen) SignalP No Known Signal Sequence Predicted analysis:

[0486] A search of the NOV32a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table32C. TABLE 32G Geneseq Results for NOV32a NOV32a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAM40496 Humanpolypeptide SEQ ID NO   3 . . . 510 202/523 (38%) 8e−91 5427 - Homosapiens. 1131 aa. 174 . . . 622 296/523 (55%) [WO200153312-A1,27-JUL-2001] AAM40495 Human polypeptide SEQ ID NO   3 . . . 510 202/523(38%) 8e−91 5426 - Homo sapiens. 1131 aa. 174 . . . 622 296/523 (55%)[WO200153312-A1, 26-JUL-2001] AAM38709 Human polypeptide SEQ ID NO   3 .. . 510 202/523 (38%) 8e−91 1854 - Homo sapiens. 1114 aa. 157 . . . 605296/523 (55%) [WO200153312-A1, 26-JUL-2001] AAB94266 Human proteinsequence SEQ ID   3 . . . 510 200/523 (38%) 4e−90 NO: 14680 - Homosapiens. 1104 157 . . . 595 292/523 (55%) aa. [EP1074617-A2.07-Feb-2001] AAB04766 Human vesicle trafficking protein-9   3 . . . 510200/523 (38%) 4e−90 (VETRP-9) protein - Homo sapiens. 157 . . . 595292/523 (55%) 1104 aa. [WO200146256-A2. 28- JUN-2001]

[0487] In a BLAST search of public sequence datbases, the NOV32a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 32D. TABLE 32D Public BLASTP Results for NOV32a NOV32a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value BAA86542 KIAA1228protein - Homo  3 . . . 510 214/523 (40%)  e−110 sapiens (Human), 843 aa135 . . . 576 316/523 (59%) (fragment). Q9ULJ2 KIAA1228 protein - Homo 3 . . . 510 214/523 (40%)  e−110 sapiens (Human). 724 aa  16 . . . 457316/523 (59%) (fragment). O94848 KIAA0747 protein - Homo  3 . . . 510202/523 (38%) 2e−90 sapiens (Human). 1072 aa 115 . . . 563 296/523 (55%)(fragment). Q9BSJ8 Similar to membrane bound C2  3 . . . 510 200/523(38%) 1e−89 domain containing protein - Homo 157 . . . 595 292/523 (55%)sapiens (Human). 1104 aa. Q91X62 Similar to membrane bound C2  3 . . .510 200/523 (38%) 1e−88 domain containing protein - Mus 147 . . . 585287/523 (54%) musculus (Mouse). 1092 aa.

[0488] PFam analysis predicts that the NOV32a protein contains thedomains shown in the Table 32E. TABLE 32E Domain Analysis of NOV32aIdentities/ Similarities NOV32a for the Pfam Match Matched Expect DomainRegion Region Value C2 237 . . . 321 33/98 (34%) 2.8e−16 60/98 (61%)

Example 33

[0489] The NOV33 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 33A. TABLE 33A NOV33 SequenceAnalysis SEQ ID NO: 77 3084 bp NOV33a,GACCCTCTCCTGCAGAGGCAGAGGCCGCCTGCCACAGGCCACGCGGAGCAGGGTCCCA CG135070-01DNA Sequence CC ATGGCCCTGAGCATCTTGACTGAGCAGTTCTGCATCCCAAGGCCTCACAAGAAGCCCCCGAGCGCCCACAGCATGAAGGAGGAGGCCTTCCTCCGGCGCCGCTTCTCCCTGTGTCCACCTTCCTCCACCCCTCAGAAAGTCGACCCCCGGAAGCTCACCCGGAACTTGCTCCTCAGCGGAGACAATGAGCTCTACCCACTCAGCCCAGGGAAGGACATGGAGCCCAACGGCCCGTCGCTGCCCAGGGATGAAGGGCCCCCGACCCCAAGCTCTGCCACGAAGGTGCCACCGGCAGAGTACAGGCTGTGCAACGGGTCAGACAAGGAATGTGTGTCCCCCACCGCCAGGGTCACCAAGAAGGAGACTCTCAAGGCGCAGAAGGAGAACTACCGGCAGGAGAAGAAGCGCGCCACACGGCAQCTGCTCAGCCCTCTGACAGACCCCAGCGTGGTCATCATCGCTGACAGCCTGAAGATCCGCGGCACCCTGAAGAGCTGGACCAAGCTGTGGTGCGTGCTGAAGCCGGGGGTGCTGCTCATCTACAAGACGCCCAAGGTGGGCCAGTGGGTGGGCACGGTGCTGCTGCACTGCTGCGAGCTCATCGAGCGGCCCTCCAAGAAGGACGGCTTCTGCTTCAAGCTCTTCCACCCGCTGGATCAGTCCGTCTGGGCCGTGAAGGGCCCCAAAGGTGAGAGCGTGGGCTCCATCACACAGCCCCTGCCCAGCAGCTACCTGATCTTCAGGGCCGCCTCCGAGTCAGATGGTCGCTGCTGGCTGGACGCCCTGGAGCTGGCCCTGCGCTGCTCTAGCCTACTGAGACTGGGCACCTGCAAGCCGGGCCGAGACGGGGAGCCAGGGACCTCGCCAGACGCATCACCCTCATCGCTCTGTGGGCTGCCACCCTCAGCCACTGTCCACCCAGACCAAGACCTGTTCCCACTGAACGGGTCTTCCCTGGAGAACGATGCATTCTCAGACAAGTCGGAGAGAGAGAACCCTGAGGAGTCAGATACCGAGACCCAGGACCATAGCCGGAAGACGGAGAGTGGCAGCGACCAGTCAGAGACCCCTGGGGCCCCCGTGCGGAGAGGGACCACCTATGTGGAGCAGGTCCAGGAGGAGCTGGGGGAGCTGGGCGAGGCGTCCCAGGTGGAGACAGTGTCAGAGGAGAACAAGAGTCTGATGTGGACCCTGCTGAAGCAGCTACGGCCAGGCATGGACCTGTCCCGCGTGGTGCTACCCACGTTCGTACTGGAGCCGCGCTCCTTCCTGAACAAGCTCTCCCACTACTACTACCACGCAGACCTGCTCTCCAGGGCTGCGGTGCAGGAGGATGCCTACAGCCGCATGAAGCTGGTGCTGCGGTGGTACCTGTCTGGCTTCTACAAGAAGCCCAAGGGAATCAACAAGCCGTACAACCCCATCCTGGGGGAGACCTTCCGCTGCTGCTGGTTCCACCCGCAGACTGACAGCCGCACATTCTACATAGCACAGCAGGTGTCCCACCACCCGCCCGTGTCTGCCTTCCACGTCAGCAACCGGAAGGACGGCTTCTGCATCAGTGGCAGCATCACACCCAAGTCCAGGTTTTATGGGAACTCGCTGTCGGCCCTGCTGGACGGCAAAGCCACCCTCACCTTCCTGAACCGAGCCGAGGATTACACCCTTACCATGCCCTACGCCCACTGCAAAGGAATCCTGTATGGCACGATGACCCTGGAGCTGGGTGGGAAGGTCACCATCGAGTGTGCGAAGAACAACTTCCAGGCCCAGCTGGAATTCAAACTCAAGCCCTTCTTCGGGGGTAGCACCAGCATCAACCACATCTCGGGAAACATCACGTCGGGAGAGGAAGTCCTGGCGAGCCTCAGTGGCCACTGGGACAGGGACGTGTTTATCAAGGAGGAAGGGAGCGGAAGCAGTGCGCTTTTCTGGACCCCGAGCGGGGAGGTCCGCAGACACAGGCTGAGGCAGCACACGGTGCCGCTGGAGGGGCAGACGGAGCTGGAGTCCGAGACGCTCTGGCAGCACGTCACCAGGGCCATCAGCAAGGGCCACCAGCACAGGGCCACACAGGAGAAGTTTGCACTCCAGGAGCCACAGCGGCAGCGGGCCCGTGAGCCGGAGGAGAGCCTCATGCCCTGGAAGCCGCAGCTGTTCCACCTGGACCCCATCACCCAGGAGTGGCACTACCGATACGAGGACCACAGCCCCTGGGACCCCCTGAAGGACATCGCCCAGTTTGAGCAAGACGGGATCCTGCGGACCTTGCAGCAGGAGGCCGTGGCCCGCCAGACCACCTTCCTGGGCAGCCCAGGGCCCAGGCACGAGAGGTCTCGCCCAGACCAGCGGCTTCGCAAGGCCAGCGACCAGCCCTCCGGCCACAGCCAGGCCACGGAGAGCAGCGGATCCACGCCTGAGTCCTGCCCAGAGCTCTCAGACGAGGAGCAGGATGGTGACTTTGTCCCTGGCGGTCAGAGCCCATGCCCTCGGTGCAGGAACGAGGCGCGGCGGCTGCAGGCCCTGCACGAGCCCATCCTCTCCATCCGAGAGGCCCAGCAGGAGCTGCACAGGCACCTCTCGGCCATGCTGAGCTCCACGGCACGGGCAGCACAGGCACCGACCCCAGGCCTCCTGCAGAGCCCCCGATCCTGGTTCCTGCTCTGCGTGTTCCTGGCGTGTCAGCTGTTCATTAACCACATCCTCAAATAG GAGCCCTCCGGGCAGAGCTCCTGGCCGGTCCTGAGCCCTCCCTCCCAGGCACCCAGCACTTTAAGCCTGCTCCATGGAGGCAGAGAGGCCCGGCAAGCACAGCCACTGTGACGGGGAGTCCAGGCGCAGGAGGGACCCGGGGCCACAAGGCGCTGCGGGCCCAGGTGTGCTGGGCCCCTCTCAGGGGCACTGGCCTCTCTCCAGGGCCTTCCGCCCAGCGCTGGCCTTAATGCTAAAGCCAAATGCAGCTTCTGCTGTGCGACCCACTCCTGGCCATCTTGCCGTGTCACCCCCTGTCCGGC CTCCACTTGCORF Start: ATG at 61 ORF Stop: TAG at 2770 SEQ ID NO: 78 903 aa MW at101214.4 kD NOV33a.MALSILTEQFCIPRPHKKPPSAHSMKEEAFLRRRFSLCPPSSTPQKVDPRKLTRNLLL CG135070-01Protein SequenceSGDNELYPLSPGKDMEPNGPSLPRDECPPTPSSATKVPPAEYRLCNGSDKECVSPTARVTKKETLKAQKENYRQEKKRATRQLLSALTDPSVVIMADSLKIRGTLKSWTKLWCVLKPGVLLIYKTPKVGQWVGTVLLHCCELIERPSKKDCFCFKLFHPLDQSVWAVKGPKGESVGSITQPLPSSYLIFRAASESDGRCWLDALELALRCSSLLRLGTCKPGRDGEPGTSPDASPSSLCCLPASATVHPDQDLFPLNGSSLENDAFSDKSERENPEESDTETQDHSRKTESGSDQSETPGAPVRRGTTYVEQVQEELGELGEASQVETVSEENKSLMWTLLKQLRPGMDLSRVVLPTFVLEPRSFLNKLSDYYYHADLLSRAAVEEDAYSRMKLVLRWYLSGFYKKPKGIKKPYNPILGETFRCCWFHPQTDSRTFYIAEQVSHHPPVSAFHVSNRKDGFCISGSITAKSRFYGNSLSALLDGKATLTFLNRAEDYTLTMPYAHCKGILYGTMTLELGGKVTIECAKNNFQAQLEFKLKPFPGGSTSINQISGKITSGEEVLASLSGHWDRDVFIKEEGSGSSALFWTPSGEVRRQRLRQHTVPLEGQTELESERLWQHVTRAISKGDQHRATQEKFALEEAQRQRARERQESLMPWKPQLFHLDPITQEWHYRYEDHSPWDPLKDIAQFEQDGILRTLQQEAVARQTTFLGSPGPRHERSGPDQRLRKASDQPSGHSQATESSGSTPESCPELSDEEQDGDFVPGGESPCPRCRKEARRLQALHEAILSIREAQQELHRHLSANLSSTARAAQAPTPGLLQSPRSWFLLCVFLACQLFTNHILK

[0490] Further analysis of the NOV33a protein yielded the followingproperties shown in Table 33B. TABLE 33B Protein Sequence PropertiesNOV33a PSort 0.8500 probability located in endoplasmic reticulumanalysis: (membrane); 0.7400 probability located in nucleus; 0.4400probability located in plasma membrane: 0.1000 probability located inmitochondria inner membrane SignalP No Known Signal Sequence Predictedanalysis:

[0491] A search of the NOV33a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table33C. TABLE 33C Geneseq Results for NOV33a NOV32a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAM40420 Humanpolypeptide SEQ ID NO  70 . . . 903 828/834 (99%) 0.0 3565 - Homosapiens. 842 aa.   9 . . . 842 830/834 (99%) [W0200153312-A1,26-JUL-2001] AAM42204 Human polypeptide SEQ ID NO 224 . . . 903 676/680(99%) 0.0 7135 - Homo sapiens. 690 aa.  11 . . . 690 679/680 (99%)[WO200153312-A1, 26-JUL-2001] ABB61239 Drosophila melanogaster 142 . . .749 337/612 (55%) 0.0 polypeptide SEQ ID NO 10509 -   1 . . . 595436/612 (71%) Drosophila melanogaster. 762 aa. [WO200171042-A2,27-SEP-2001] AAB98084 Human protein sequence SEQ ID 406 . . . 903268/498 (53%) e−155 NO:110 - Homo sapiens. 472 aa.   1 . . . 472 350/498(69%) [WO200130972-A2, 03-May-2001] AAB98083 Human brain eDNA libraryprotein 406 . . . 792 244/387 (63%) e−149 sapiens. 385 aa. [WO200130972-  1 . . . 383 304/387 (78%) A2, 03-May-2001] 

[0492] In a BLAST search of public sequence datbases, the NOV33a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 33D. TABLE 33D Public BLASTP Results for NOV33a NOV33a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q9H0X9 Oxysterolbinding protein-related 25 . . . 903 878/879 (99%) 0.0 protein 5(OSBP-related protein 5)  1 . . . 879 878/879 (99%) (ORP-5) - Homosapiens (Human). 879 aa. Q9ER64 Oxysterol binding protein-related 25 . .. 903 744/880 (84%) 0.0 protein 5 (OSBP-related protein 5)  1 . . . 874794/880 (89%) (ORP-5) (Oxystyrol-binding protein homologue 1) - Musmusculus (Mouse), 874 aa. Q8R510 Oxysterol binding protein 25 . . . 903743/880 (84%) 0.0 homologue 1 - Mus musculus  1 . . . 874 794/880 (89%)(Mouse). 874 aa. BAA95975 KIAA1451 protein - Homo sapiens 41 . . . 903484/892 (54%) 0.0 (Human). 954 aa (fragment). 97 . . . 954 624/892 (69%)Q8WXP8 Oxysterol-binding protein-like 41 . . . 903 484/892 (54%) 0.0protein OSBPL8 - Homo sapiens 32 . . . 889 624/892 (69%) (Human). 889aa.

[0493] PFam analysis predicts that the NOV33a protein contains thedomains shown in the Table 33E. TABLE 33E Domain Analysis of NOV33aNOV33a Identities/ Pfam Match Similarities Expect Domain Region for theMatched Region Value PH 151 . . . 267 29/117 (25%) 2.3e−13 86/117 (74%)Oxysterol_BP 362 . . . 778 118/447 (26%)  1.3e−55 258/447 (58%) 

Example 34

[0494] The NOV34 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 34A. TABLE 34A NOV34 SequenceAnalysis SEQ ID NO: 79 1905 bp NOV34a.GTCGACGCGGCCGCGCTGCGTCCAGCATTGGATATTTGTCAGGAATGCAGATACCCTG CG172478-01DNA Sequence AAGGGAACACAACA ATGGTCCAAGGGGGTTTCCCAGAAAAAATCAGACAAAGATATGCAGATCTGCCTGGAGAACTGCACATTATTGAACTTGAAAAAGATAAGAATGGACTTGGACTCAGCCTTGCTGGTAATAAAGACCGATCACGCATGAGCATATTTGTGGTGGGAATTAACCCGGAAGGACCTGCTGCCGCAGATGGACGAATGCATATTGGAGATGAACTCTTAGAGATAAACAATCAGATTCTGTATGGAAGAAGTCACCAAAATGCATCTGCCATTATTAAGACTGCCCCATCAAAGGTCAAGCTGGTTTTCATCAGAAACGAGGATGCAGTCAATCAGATGGCCGTTACTCCCTTTCCAGTGCCATCAAGTTCTCCATCTTCTATTGAGGATCAGAGCGGCACCGAACCTATTAGTAGTGAGGAAGATGGCAGCCTCGAAGTTGGTATTAAACAATTGCCTGAAAGTGAAAGCTTCAAACTGGCTGTCAGCCAGATGAAACAGCAAAAATATCCAACAAAAGTCTCCTTCAGTTCACAAGAGATACCATTAGCACCAGCTTCATCATACCATTCAACAGATCCAGACTTCACAGGCTATGGTGGTTTCCAGGCTCCTCTGTCAGTGGACCCCGCAACGTGTCCCATTGTCCCTGGACAGGAAATGATTATAGAAATATCCAAGGGACGTTCAGGGCTTGGTCTCAGCATTGTGGGAGGAAAAGACACACCCTTGTTCTGGAGGCTGGGAAGTCCAAGAGCATGGAGCCAGCATCTGGTGAGGGCCTTCATGCTGCATCATCCTGTGACAGAAGTTCAAGGGCAAAATGCTATAGTTATCCATGAAGTCTATGAAGAAGGGGCAGCAGCCAGAGATGGAAGACTTTGGGCTGGTGACCAGATATTAGAGGTTAATGGGGTTGACCTGAGGAACTCCAGCCACGAAGAAGCCATCACAGCCCTGAGGCAGACCCCCCAGAAGGTGCGGCTGGTGGTGTATAGAGATGAGGCACACTACCGGGATGAGGAGAACTTGGAGATTTTCCCTGTGGATCTGCAGAAGAAAGCTGGCCGGGGCCTGGGCCTGAGCATCGTTGGGAAACGGAATGGAAGCGGAGTGTTTATTTCTGACATCGTGAAAGGCGGAGCCGCAGACCTGGATGGGAGATTGATTCAGGGAGATCAGATCTTATCTCTGAATGGGGAGGACATGAGAAATCCCTCACAGCAGACAGTGGCCACCATCCTCAAGTGTGCACAGGGACTTGTGCAGCTAGAGATTGGAAGACTCCGAGCTGGTTCCTGGACCTCCGCAACCACGACATCACAGAACAGTCAGGGTAGTCAGCAGAGTGCACACAGCAGCTGTCATCCCTCCTTCGCTCCTGTCATCACTGGCCTGCAAAACCTGGTTGCCACAAAAAGAGTTTCAGATCCTTCCCAGAAAACAGATATGGAACCAAGGACTGTTGAGATAAACAGGGAGCTCAGTGATGCCCTTGGAATCAGTATTGCTGGAGGAAGAGGAAGTCCCTTAGGAGATATCCCCGTATTTATTGCCATGATTCAGGCTAGCGGAGTGGCCGCACGGACACAGAAGCTTAAAGTAGGAGATCGGATTGTCAGCATTAACGGGCAACCTTTGGATGGGCTGTCTCACGCGGATGTGGTTAATCTGCTGAAGAACGCCTACGGGCGCATTATCCTGCAGGTAGTAGCAGATACCAATATAAGCGCCATAGCAGCTCAGCTTGAAAACATGTCTACAGGCTACCACCTTGGTTCGCCCACTGCTGAACACCATCCAGAAGACACAGAGTGA GTATTTCAGATGCAGAGG ORF Start: ATG at 73ORF Stop TGA at 1885 SEQ ID NO: 80 604 aa MW at 64963.5 kD NOV34a.MVQCCFPEKIRQRYADLPGELHIIELEKDKNGLGLSLAGNKDRSRMSIFVVGINPEGP CG172478-01Protein SequenceAAADGRMHIGDELLEINNQILYGRSHQNASAIIKTAPSKVKLVFIRNEDAVNQMAVTPFPVPSSSPSSIEDQSGTEPISSEEDCSLEVGIKQLPESESFKLAVSQMKQQKYPTKVSFSSQEIPLAPASSYHSTDADFTGYGGFQAPLSVDPATCPIVPGQEMIIEISKGRSGLGLSIVGGKDTRLFWRLGSPRAWSQHLVRAFMLHHPVTEVEGQNAIVIHEVYEEGAAARDGRLWAGDQILEVNGVDLRNSSHEEAITALRQTPQKVRLVVYRDEAHYRDEENLEIFPVDLQKKAGRGLGLSIVGKRNGSGVFISDIVKCGAADLDGRLIQGDQILSVNGEDMRNASQETVATILKCAQGLVQLEIGRLRAGSWTSARTTSQNSQGSQQSAHSSCHPSFAPVITGLQNLVGTKRVSDPSQKTDMEPRTVEINRELSDALGISIAGGRGSPLGDIPVFTAMIQASGVAARTQKLKVGDRIVSINGQPLDGLSHADVVNLLKNAYGRIILQVVADTNISAIAAQLENMSTGYHLGSPTAEHHPEDTE

[0495] Further analysis of the NOV34a protein yielded the followingproperties shown in Table 34B. TABLE 34B Protein Sequence PropertiesNOV34a PSort 0.6500 probability located in cytoplasm: 0.1000 analysis:probability located in mitochondrial matrix space: 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0496] A search of the NOV34a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table34C. TABLE 34C Geneseq Results for NOV34a NOV34a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length Match the MatchedExpect Identifier [Patent #, Date] Residues Region Value AAY24025 Aminoacid sequence of the human  8 . . . 604 566/600 (94%) 0.0 MMSC1protein - Homo sapiens. 1224 . . . 1793 567/600 (94%) 1881 aa.[WO9936566-A1. 22 Jul. 1999] ABG06117 Novel human diagnostic protein  8. . . 409 400/402 (99%) 0.0 #6108 - Homo sapiens. 1627 aa. 1226 . . .1627 401/402 (99%) [WO200175067-A2. 11 Oct. 2001] ABG06117 Novel humandiagnostic protein  8 . . . 409 400/402 (99%) 0.0 #6108 - Homo sapiens.1627 aa. 1226 . . . 1627 401/402 (99%) [WO200175067-A2. 11 Oct. 2001]ABG07290 Novel human diagnostic protein  8 . . . 366 357/359 (99%) 0.0#7281 - Homo sapiens. 1584 aa. 1226 . . . 1584 358/359 (99%)[WO200175067-A2. 11 Oct. 2001] ABG07290 Novel human diagnostic protein 8 . . . 366 357/359 (99%) 0.0 #7281 - Homo sapiens. 1584 aa. 1226 . . .1584 358/359 (99%) [WO200175067-A2. 11 Oct. 2001]

[0497] In a BLAST search of public sequence datbases, the NOV34a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 34D. TABLE 34D Public BLASTP Results for NOV34a NOV34a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value AAM28433PalsI-associated tight junction  8 . . . 604 563/600 (93%) 0.0 protein -Homo sapiens (Human), 1224 . . . 1793 566/600 (93%) 1801 aa. O70471Channel interacting PDZ domain  1 . . . 604 492/636 (77%) 0.0 protein -Mus musculus (Mouse).  1 . . . 604 518/636 (81%) 612 aa. Q9H3N9 PDZdomain protein 3′ variant 4 -  8 . . . 455 410/453 (90%) 0.0 Homosapiens (Human). 1134 aa.  683 . . . 1105 413/453 (90%) O43742 InadIprotein - Homo sapiens  8 . . . 366 357/359 (99%) 0.0 (Human), 1582 aa.1224 . . . 1582 358/359 (99%) Q8WU78 Similar to channel-interacting 274. . . 604 331/334 (99%) 0.0 PDZ domain protein - Homo  5 . . . 338331/334 (99%) sapiens (Human). 346 aa (fragment).

[0498] PFam analysis predicts that the NOV34a protein contains thedomains shown in the Table 34E. TABLE 34E Domain Analysis of NOV34aIdentities/ Similarities Pfam NOV34a Match for the Matched Domain RegionRegion Expect Value PDZ  23 . . . 105 31/86 (36%) 5.7e−14 63/86 (73%)PDZ 219 . . . 333 40/116 (34%)  2.8e−20 89/116 (77%)  PDZ 347 . . . 42834/84 (40%) 3.5e−18 67/84 (80%) PDZ 487 . . . 572 26/88 (30%) 6.7e−1365/88 (74%)

Example 35

[0499] The NOV35 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 35A. TABLE 35A NOV35 SequenceAnalysis SEQ ID NO: 81 1563 bp NOV35a.ACCAGTTTTTCCCCAGCACCACCATCAAGGCCTCGAGGCTCCCACCTCCCTCTACAGC CG172549-01DNA Sequence CTGTGGACTCACTTAGGGAATCCCGAACG ATGACAGAAAAGGAGGTGCTGGAGTCCCCTAAGCCCTCCTTCCCAGCAGAGACTCGGCAAACTGGGCTACAGCGGCTAAAGCAGTTACTCAGGAAGGGTTCTACAGGGACAAAGGAGATGGAACTTCCCCCAGAGCCCCAGGCCAATGGGGAGGCAGTGGGAGCTGGGGGTGGGCCCATCTACTACATCTATGAGGAAGAGGAAGAGGAAGAAGAGGAGGAGGAGGAGCCACCCCCAGAACCTCCTAAGCTGGTCAACGATAAGCCCCACAAATTCAAAGATCACTTCTTCAAGAAGCCAAAGTTCTGTGATGTCTGTGCCCGGATGATTGTTCTCAACAACAAGTTTGGGCTTCGCTGTAAGAACTGCAAAACCAACATCCATGAACACTGTCAGTCCTATGTGGAAATGCAGAGATGCTTCGGCAAGATCCCACCTGGTTTCCATCGGGCCTATAGTTCCCCACTCTACAGCAACCAGCAGTACGCTTGTGTCAAAGATCTCTCTGCTGCCAATCGCAATGATCCTGTGTTTGAAACCCTGCGCACTGGGGTGATCATGGCAAACAAGGAACGGAAGAAGGGACAGGCAGATAAGAAAAATCCTGTAGCAGCCATGATGGAGGAGGAGCCAGAGTCGGCCAGACCAGACGAAGGCAAACCCCAGGATGGAAACCCTGAAGGGGATAACAAGGCTGAGAAGAAGACACCTGATGACAAGCACAAGCAGCCTGGCTTCCAGCAGTCTCATTACTTTGTGGCTCTCTATCGGTTCAAAGCCCTGGAGAAGGACGATCTCGATTTCCCGCCAGGAGAGAAGATCACAGTCATTGATCACTCCAATGAAGAATGGTGGCGGGGGAAAATCGGGGAGAAGGTCGGATTTTTCCCTCCAAACTTCATCATTCGGGTCCGGGCTGGAGAACGTGTGCACCGCGTGACCAGATCCTTCGTGGGGAACCGCGAGATAGGGCAGATCACTCTCAAGAAGGACCAGATCGTGGTGCAGAAAGGAGACGAAGCGGGCGGCTACGTCAAGGTCTACACCGGCCGCAAGGTGGGGCTGTTTCCCACCGACTTTCTAGAGGAAATTTAG GCGTGCGGGCGCCTGCAAGCGGGAGACACCCACACCCCATTCTGGGCGGGCCCAGTGGAGTTTGGGGAGGGGGGCGAAAGCAACGGGACTGCTGGGAGAGGAGGGGTAGGAAGGCCCGCCTGAGCGCGACGGGGCTTCCGGGAAGGGACTGGTTCTCGCCCCCTTCCCCAGCCTGGGGCCTCGGATACCTGCTGCCCAGAGCAGCCCGGACCCGAAACCTTTCAGGCCCCGCTTGCAAGAGCTGGAAAAAAACGCGTATCTACTAGGAGGAGCCAGGGACTGGGGCGGGGGGCGGGGGCGAGGGAGGGCGAACTGTCGAATGTTGCGAATTTATTAAACTTTTGACAAAACTTAAAAAAAAAAAAAAAAAAAAAAAAAAAA ORF Start: ATGat 88 ORF Stop: TAG at 1180 SEQ ID NO: 82 364 aa MW at 41506.7 kDNOV35a. MTEKEVLESPKPSFPAETRQSGLQRLKQLLRKGSTGTKEMELPPEPQANGEAVGAGGGCG172549-01 Protein SequencePIYYIYEEEEEEEEEEEEPPPEPPKLVNDKPHKFKDHFFKKPKFCDVCARMIVLNNKFGLRCKNCKTNIHEHCQSYVEMQRCFGKIPPGFHRAYSSPLYSNQQYACVKDLSAANRNDPVFETLRTGVIMANKERKKGQADKKNPVAANMEEEPESARPEEGKPQDGNPEGDKKAEKKTPDDKHKQPGFQQSHYFVALYRFKALEKDDLDFPPGEKITVIDDSNEEWWRGKIGEKVGFFPPNFIIRVRAGERVHRVTRSFVGNREIGQITLKKDQIVVQKGDEAGGYVKVYTGRKVGLFPTDFLEEI SEQ ID NO: 83 1563 bp NOV35b.ACCACTTTTTCCCCAGCACCACCATCAAGGCCTCGAGGCTCCCAGCTCCCTCTACAGC CG172549-02DNA Sequence CTGTGGACTGACTTAGGGAATCCCGAACG ATGACAGAAAAGGAGGTGCTGGAGTCCCCTAAGCCCTCCTTCCCAGCAGAGACTCGGCAAAGTGGGCTACAGCGGCTAAAGCAGTTACTCAGGAAGGGTTCTACAGGGACAAAGGAGATGGAACTTCCCCCAGAGCCCCAGGCCAATGGGGAGGCAGTGGGAGCTGGGGGTGGGCCCATCTACTACATCTATGAGGAAGAGGAAGAGGAAGAAGAGGAGGAGGAGGAGCCACCCCCAGAACCTCCTAAGCTGGTCAACGATAAGCCCCACAAATTCAAAGATCACTTCTTCAAGAAGCCAAAGTTCTGTGATGTCTGTGCCCGGATGATTGTTCTCAACAACAAGTTTGGGCTTCGCTGTAAGAACTGCAAAACCAACATCCATGAACACTGTCAGTCCTATGTGGAAATGCAGAGATGCTTCGGCAAGATCCCACCTGGTTTCCATCGGGCCTATAGTTCCCCACTCTACAGCAACCAGCAGTACGCTTGTGTCAAAGATCTCTCTGCTGCCAATCGCAATGATCCTGTGTTTGAAACCCTGCCCACTGGGGTGATCATGGCAAACAAGGAACGGAAGAAGGGACAGGCAGATAAGAAAAATCCTGTAGCAGCCATGATGGAGGAGGAGCCAGAGTCGGCCAGACCAGAGGAAGGCAAACCCCAGGATGGAAACCCTGAAGGGGATAAGAAGGCTGAGAAGAAGACACCTGATGACAAGCACAAGCAGCCTGGCTTCCAGCAGTCTCATTACTTTGTGGCTCTCTATCGGTTCAAAGCCCTGGAGAAGGACGATCTGGATTTCCCGCCAGGAGAGAACATCACAGTCATTGATGACTCCAATGAAGAATGGTGGCGGGGGAAAATCGGGGAGAAGGTCGCATTTTTCCCTCCAAACTTCATCATTCGGGTCCGGGCTGGAGAACGTGTGCACCGCGTGACGAGATCCTTCCTGGGGAACCGCGAGATAGGGCAGATCACTCTCAAGAAGGACCAGATCCTGGTGCAGAAAGGAGACGAAGCGGGCGGCTACGTCAAGGTCTACACCGGCCGCAAGGTGGGGCTGTTTCCCACCGACTTTCTAGAGGAAATTTAG GCGTGCGGGCGCCTGCAAGCGGGAGACACCCACACCCCATTCTGGGCGGGCCCAGTGGAGTTTGGGGAGGGGGGCGAAAGCAACGGGACTGCTGGGAGAGGAGGGGTAGGAAGGCCCGCCTGAGCGCGACGGGGCTTCCGGGAAGGGACTGGTTCTCGCCCCCTTCCCCAGCCTGGGGCCTCGGATACCTGCTGCCCAGAGCAGCCCGGACCCGAAACCTTTCAGGCCCCGCTTGCAAGAGCTGGAAAAAAACGCGTATCTACTAGGAGGAGCCAGGGACTGGGGCGGGGGGCGGGGGCGAGGGAGGGCGAACTGTCGAATGTTGCGAATTTATTAAACTTTTGACAAAACTTAAAAAAAAAAAAAAAAAAAAAAAAAAAA ORF Start: ATGat 88 ORF Stop: TAG at 1180 SEQ ID NO: 84 364 aa MW at 41506.7 kDNOV35b, MTEKEVLESPKPSFPAETRQSGLQRLKQLLRKGSTGTKEMELPPEPQANGEAVGAGGGCG172549-02 Protein SequencePIYYIYEEEEEEEEEEEEPPPEPPKLVNDKPHKFKDHFFKKPKFCDVCARMIVLNNKFGLRCKNCKTNIHEHCQSYVEMQRCFGKIPPGFHRAYSSPLYSNQQYACVKDLSAANRNDPVFETLRTGVIMANKERKKGQADKKNPVAAMMEEEPESARPEEGKPQDGNPEGDKKAEKKTPDDKHKQPGFQQSHYFVALYRFKALEKDDLDFPPGEKITVIDDSNEEWWRGKIGEKVGFFPPNFIIRVRAGERVHRVTRSFVGNREIGQITLKKDQIVVQKGDEAGGYVKVYTGRKVGLFPTDFLEEI

[0500] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 35B. TABLE 35BComparison of NOV35a against NOV35b. Identities/ NOV35a Residues/Similarities Match for the Protein Sequence Residues Matched RegionNOV35b 1 . . . 364 315/364 (86%) 1 . . . 364 315/364 (86%)

[0501] Further analysis of the NOV35a protein yielded the followingproperties shown in Table 35C. TABLE 35C Protein Sequence PropertiesNOV35a PSort 0.3000 probability located in nucleus: 0.1000 analysis:probability located in mitochondrial matrix space: 0.1000 probabilitylocated in lysosome (lumen): 0.0000 probability located in endoplasmicreticulum (membrane) SignalP No Known Signal Sequence Predictedanalysis:

[0502] A search of the NOV35a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table35D. TABLE 35D Geneseq Results for NOV35a NOV32a Identities/ Residues/Similarities for Geneseq Protein/Organism/Length [Patent Match theMatched Expect Identifier #, Date] Residues Region Value AAU27731 Mousefull-length polypeptide   1 . . . 364 364/364 (100%) 0.0 sequence #56 -Mus musculus, 364   1 . . . 364 364/364 (100%) aa. [WO200164834-A2.07-SEP-2001] AAU27903 Mouse contig polypeptide 112 . . . 302 188/44(98%) e-111 sequence #56 - Mus musculus, 227  33 . . . 223 189/44 (98%)aa. [WO200164834-A2. 07-SEP-2001] AAW59642 Amino acid sequence of human  4 . . . 364 143/398 (35%) 1e-61 Stac protein - Homo sapiens, 402  17 .. . 402 209/398 (51%) aa. [JP10175998-A. 30-JUN-1998] AAW59641 Aminoacid sequence of mouse  86 . . . 364 123/301 (40%) 2e-60 Stac protein -Mus sp. 403 aa. 105 . . . 403 177/301 (57%) [JP10175998-A. 30-JUN-1998]AAM82743 Human immune/haematopoietic 129 . . . 235 100/107 (93%) 3e-55antigen SEQ ID NO:10336 - Homo   3 . . . 109 104/107 (96%) sapiens, 153aa. [WO200157182- A2. 09-AUG-2001]

[0503] In a BLAST search of public sequence datbases, the NOV35a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 35E. TABLE 35E Public BLASTP Results forNOV35a NOV35a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value Q96MF2 CDNAFLJ32451 fis. clone  1 . . . 364  364/364 (100%) 0.0 SKMUS2001668.weakly similar to  1 . . . 364  364/364 (100%) neuron-specific signaltrunduction protein Stac - Homo sapiens (Human). 364 aa. Q96HU5 Similarto src homology three (SH3)  40 . . . 364  325/325 (100%) 0.0 andcysteine rich domain - Homo  1 . . . 325  325/325 (100%) sapiens(Human). 325 aa. Q99469 Stac protein (SRC homology 3 and  4 . . . 364143/398 (35%) 3e−61 cysteine-rich domain protein) -  17 . . . 402209/398 (51%) Homo sapiens (Human). 402 aa. Q8WUK8 Src homology three(SH3) and  4 . . . 364 143/398 (35%) 6e−61 cysteine rich domain - Homo 17 . . . 402 208/398 (51%) sapiens (Human). 402 aa. P97306 Stac protein(SRC homology 3 and  86 . . . 364 123/301 (40%) 4e−60 cysteine-richdomain protein) - Mus 105 . . . 403 177/301 (57%) musculus (Mouse), 403aa.

[0504] PFam analysis predicts that the NOV35a protein contains thedomains shown in the Table 35F. TABLE 35F Domain Analysis of NOV35aIdentities/ Similarities NOV35a Match for the Matched Pfam Domain RegionRegion Expect Value DC1 101 . . . 132 11/47 (23%) 0.16 21/47 (45%)DAG_PE-bind  90 . . . 140 21/52 (40%) 1.1e−10 41/52 (79%) SH3 250 . . .304 22/58 (38%) 1.8e−14 43/58 (74%)

Example 36

[0505] The NOV36 clone was analyzed, and the nucleotide and encodedpolypeptide sequences are shown in Table 36A. TABLE 36A NOV36 SequenceAnalysis SEQ ID NO: 85 442 bp NOV36a.CCGGCGGCTGTTGTCGGGCCTCCAGCGGGCGGGGCCGTTGGCGGAGCAGAGCGGAGGC CG59828-01DNA Sequence GCACCCGGGCGGAGGGCCCACGAGGGCTCAGCCTTCCCGGTCAGCGGTCCTGACGGTATCCCAGAGTGCCAGAGAACCGTTGCTTTTCCGAGTTGCTCTTCTTCCAGGCTCCGTTG GTGGTCCGCATGGCCCGTGGAAATCAACGAGAACTTGCCCGCCAGAAAAACATGAAGAAAACCCAGGAAATTAGCAAGGGAAAGAGGAAAGAGGATAGCTTGACTGCCTCTCAGAGAAAGCAGAGTTCTGGAGGCCAGAAATCTGAGAGCAAGATCTCAGCTGGGCCACACCTCCCTCTGAAGGCTCCAAGGGAGAATCCTTGCTTTCCTCTTCCAGCTGCTGGTGGCTCCAGGTATTACTTGGCTTATGGCAGCATAACTCCTATCTCTGCCTTTGTCTTTGTGGTCTTCTTTTCTGTCTTCTTCCCTTCTTTTTATGAGCACTTTTGCTGTTGGATTTAG GTTCCATTCTAACCTAGGATGATCTCATTTGGAAATCCTTAATTTCATCTACAAAAACTGTTTTCCCAAATAGGTCACATTCACGCATATCAGATGGACAGATGTATCATTTTGGGGTCCACCATTCAACCCACTACAAGGAGTTTTTTAAACAAAAATAGGAAACTTAGATGTAACTTAGCACTTTTTTTTTTTTTTTTTGAGATGGAGTCTCACTCTGTCACCAGACTGGAGTGCAGTGGCGCCATCTCAGCTCCATGCAACCTCTGCCTCCTGGGTTCAACCAGTTCTCTTGCCTCAGCCTCCTGGGTAGCTGGGATTACAGGCACGCGCTGCCACACCCAGGTAATTTATTTATTTTTTTTTTGAGACAGAGTCTCGCACTGTTGCCCAGGCTGGACTGCAGTGGCGTGATCTCTGCTCACTGCAACCTCCGCCTCCCGGGTTCAAGCGATTCTCCAGCCTCAGCTTCCTGAGTAGATGGGATTACAGGCGCCTGCCACCACGCCCAGCTAATTTTTTTGTATTCTTAGTAGACATGGGGTTTCACCATGTTGGCCAGGCTGGTCTCCATCTCCTCACCTCGTGATTCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGTCACAGCCCCCGGCCATAATTTAGCACTTTAAAAAATAATAGCCATGTTGGGCCAGCCGTGGTGGCTCATGCCTGTAATCTGAGCACTTTCGCAGACCAAGGCGGGTAGATCCCTTGTGCCCAGGAGTTCAAGACCAGCCTGGGCAACATGGCGAAACCCCATTTCTACTAAAAATACAAAAATTAGCTGGGGCGAGGGGATAGGCCGAGTTCCGGGTGTAAGGGGGCCATTAGGGAGAGCAGAGCGAGGCAGCTGATCTTCCGGATTGGGGGCCTTGCCCGGAAGCTGGACCTCACGGAGATGAAACGGAAGATGCACCAGGATATGATCTCCATACAGAACTTTCTCATCTACGTGGCCCTGCTGCGAGTCACTCCATTTATCTTAAAGAAATTGGACAGCATATGAAGATTGGACATCACATGTGAATGCATGATATGAACAGCCTGGTTACAGTTTCTACTGTTCTCTGCAAGTAAATAGGCCCACAAAGGTATAAGAGACTCTTTGAATCCACATAAAAATTCTGCTTGTTAAGAACAAGTTGAGCTCTGGTAACTGATCTTAATAGCTAAAATATAAAAATATTTGGGAAGTCTGAAATCAGGTCTCCTGGCCCTGGTGTGCCCTTAATGCCTGTGACAGTTGGCCTCTGTGAATATTGGTATAATTGTAAATAATGTCAAACTCCATTTTCTACCAAGTATTAATTAAGGGAAGTATGTCTCAGAAATGGCAAAAAAAAAAAAAAAAAAAAAA ORF Start: ATG at184 ORF Stop: TAG at 514 SEQ ID NO: 86 110 aa MW at 12349.1 kD NOV36a.MARCNQRELARQKNMKKTQEISKGKRKEDSLTASQRKQSSCCQKSESKMSAGPHLPLK CG59828-01Protein Sequence APRENPCFPLPAAGGSRYYLAYGSITPISAFVFVVFFSVFFPSFYEDFCCWISEQ ID NO 87 255 bp NOV36b.GGATCCGCCCGTGGAAATCAACGAGAACTTGTCCGCCAGAAAAACATGAAGAAAACCC 172146552 DNASequence AGGAAATTAGCAAGGGAAAGAGGAAAGAGGATAGCTTGACTCCCTCTCAGAGAAAGCAGAGTTCTCGAGGCCACAAATCTCACAGCAACATGTCAGCTGGGCCACACCTCCCTCTGGAGGCTCCAAGGGAGAATCCTTGCTTTCCTCTTCCAGCTGCTGGTGGCTACAGGTATTACTTGCCTTATGGCAGCCTCGAG ORF Start: at 1 ORF Stop: end of sequence SEQ IDNO: 88 85 aa MW at 9368.5 kD NOV36b.GSARGNQRELVRQKNMKKTQETSKGKRKEDSLTASQRKQSSCGQKSESKMSAGPHLPL 172146552Protein Sequence EAPRENPCFPLPAAGGYRYYLAYGSLE

[0506] Sequence comparison of the above protein sequences yields thefollowing sequence relationships shown in Table 36B. TABLE 36BComparison of NOV36a against NOV36b. Identities/ NOV36a Residues/Similarities Match for the Protein Sequence Residues Matched RegionNOV36b 2 . . . 69 49/68 (72%) 3 . . . 70 50/68 (73%)

[0507] Further analysis of the NOV36a protein yielded the followingproperties shown in Table 36C. TABLE 36C Protein Sequence PropertiesNOV36a PSort 0.8500 probability located in endoplasmic reticulumanalysis: (membrane): 0.5852 probability located in microbody(peroxisome): 0.4400 probability located in plasma membrane; 0.1000probability located in mitochondrial inner membrane SignalP No KnownSignal Sequence Predicted analysis:

[0508] A search of the NOV36a protein against the Geneseq database, aproprietary database that contains sequences published in patents andpatent publication, yielded several homologous proteins shown in Table36D. TABLE 36D Geneseq Results for NOV36a Identities/ NOV36aSimilarities Residues/ for the Geneseq Protein/Organism/Length [PatentMatch Matched Expect Identifier #, Date] Residues Region Value ABG20531Novel human diagnostic protein 4 . . . 51 37/48 (77%) 8e−13 #20522 -Homo sapiens. 121 aa. 63 . . . 110 39/48 (81%) [WO200175067-A2, 11 Oct.2001] ABG20531 Novel human diagnostic protein 4 . . . 51 37/48 (77%)8e−13 #20522 - Homo sapiens. 121 aa. 63 . . . 110 39/48 (81%)[WO200175067-A2, 11 Oct. 2001] ABG20532 Novel human diagnostic protein 1. . . 63 36/63 (57%) 6e−11 #20523 - Homo sapiens, 104 aa. 25 . . . 86 45/63 (71%) [WO200175067-A2, 11 Oct. 2001] ABG20532 Novel humandiagnostic protein 1 . . . 63 36/63 (57%) 6e−11 #20523 - Homo sapiens.104 aa. 25 . . . 86  45/63 (71%) [WO200175067-A2. 11 Oct. 2001] AAU29730Novel human secreted protein #221 - 40 . . . 90  31/51 (60%) 8e−11 Homosapiens. 71 aa. 10 . . . 60  37/51 (71%) [WO200179449-A2. 25 Oct. 2001]

[0509] In a BLAST search of public sequence datbases, the NOV36a proteinwas found to have homology to the proteins shown in the BLASTP data inTable 36E. TABLE 36E Public BLASTP Results for NOV36a NOV36a Identities/Protein Residues/ Similarities for Accession Match the Matched ExpectNumber Protein/Organism/Length Residues Portion Value O75920 SmallEDRK-rich factor 1, long 1 . . . 110 110/110 (100%)  5e−60 isoform -Homo sapiens (Human), 1 . . . 110 110/110 (100%)  110 aa. O75919 SmallEDRK-rich factor 1, short 1 . . . 51  40/51 (78%) 4e−14 isoform (SmallEDRK-rich factor 1 . . . 51  42/51 (81%) 1A) (Telomeric) - Homo sapiens(Human). 62 aa. O88892 4F5 (Small EDRK-rich factor 1) - 1 . . . 38 37/38 (97%) 2e−13 Mus musculus (Mouse). 62 aa. 1 . . . 38  38/38 (99%)O75918 Small EDRK-rich factor 2 - Homo 1 . . . 38  26/38 (68%) 2e−07sapiens (Human). 59 aa. 1 . . . 38  31/38 (81%) Q9VEW2 CG17931 protein -Drosophila 1 . . . 37  24/37 (64%) 2e−05 melanogaster (Fruit fly). 60aa. 1 . . . 36  29/37 (77%)

[0510] PFam analysis predicts that the NOV36a protein contains thedomains shown in the Table 36F. TABLE 36F Domain Analvsis of NOV36a PfamDomain NOV36a Match Region Identities/ Expect Similarities Value for theMatched Region

Example B Sequencing Methodology and Identification of NOVX Clones

[0511] 1. GeneCalling™ Technology: This is a proprietary method ofperforming differential gene expression profiling between two or moresamples developed at CuraGen and described by Shimkets, et al., “Geneexpression analysis by transcript profiling coupled to a gene databasequery” Nature Biotechnology 17:198-803 (1999). cDNA was derived fromvarious human samples representing multiple tissue types, normal anddiseased states, physiological states, and developmental states fromdifferent donors. Samples were obtained as whole tissues primary cellsor tissue cultured primary cells or cell lines. Cells and cell lines mayhave been treated with biological or chemical agents that regulate geneexpression, for example, growth factors, chemokines or steroids. ThecDNA thus derived was then digested with up to as many as 120 pairs ofrestriction enzymes and pairs of linker-adaptors specific for each pairof restriction enzymes were ligated to the appropriate end. Therestriction digestion generates a mixture of unique cDNA gene fragments.Limited PCR amplification is performed with primers homologous to thelinker adapter sequence where one primer is biotinylated and the otheris fluorescently labeled. The doubly labeled material is isolated andthe fluorescently labeled single strand is resolved by capillary gelelectrophoresis. A computer algorithm compares the electropherogramsfrom an experimental and control group for each of the restrictiondigestions. This and additional sequence-derived information is used topredict the identity of each differentially expressed gene fragmentusing a variety of genetic databases. The identity of the gene fragmentis confirmed by additional, gene-specific competitive PCR or byisolation and sequencing of the gene fragment.

[0512] 2. SeqCalling™ Technology: cDNA was derived from various humansamples representing multiple tissue types, normal and diseased states,physiological states, and developmental states from different donors.Samples were obtained as whole tissue, primary cells or tissue culturedprimary cells or cell lines. Cells and cell lines may have been treatedwith biological or chemical agents that regulate gene expression, forexample, growth factors, chemokines or steroids. The cDNA thus derivedwas then sequenced using CuraGen's proprietary SeqCalling technology.Sequence traces were evaluated manually and edited for corrections ifappropriate. cDNA sequences from all samples were assembled together,sometimes including public human sequences, using bioinformatic programsto produce a consensus sequence for each assembly. Each assembly isincluded in CuraGen Corporation's database. Sequences were included ascomponents for assembly when the extent of identity with anothercomponent was at least 95% over 50 bp. Each assembly represents a geneor portion thereof and includes information on variants, such as spliceforms single nucleotide polymorphisms (SNPs), insertions, deletions andother sequence variations.

[0513] 3. PathCalling™ Technology: The NOVX nucleic acid sequences arederived by laboratory screening of cDNA library by the two-hybridapproach, cDNA fragments covering either the full length of the DNAsequence, or part of the sequence, or both, are sequenced. In silicoprediction was based on sequences available in CuraGen Corporation'sproprietary sequence databases or in the public human sequencedatabases, and provided either the full length DNA sequence, or someportion thereof.

[0514] The laboratory screening was performed using the methodssummarized below:

[0515] cDNA libraries were derived from various human samplesrepresenting multiple tissue types, normal and diseased states,physiological states, and developmental states from different donors.Samples were obtained as whole tissue, primary cells or tissue culturedprimary cells or cell lines. Cells and cell lines may have been treatedwith biological or chemical agents that regulate gene expression, forexample, growth factors, chemokines or steroids. The cDNA thus derivedwas then directionally cloned into the appropriate two-hybrid vector(Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as wellas commercially available cDNA libraries from Clontech (Palo Alto,Calif.) were then transferred from E.coli into a CuraGen Corporationproprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and6,083,693, incorporated herein by reference in their entireties).

[0516] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportionproprietary library of human sequences was used to screen multipleGal4-AD fusion cDNA libraries resulting in the selection of yeast hybriddiploids in each of which the Gal4-AD fusion contains an individualcDNA. Each sample was amplified using the polymerase chain reaction(PCR) using non-specific primers at the cDNA insert boundaries. Such PCRproduct was sequenced; sequence traces were evaluated manually andedited for corrections if appropriate. cDNA sequences from all sampleswere assembled together, sometimes including public human sequences,using bioinformatic programs to produce a consensus sequence for eachassembly. Each assembly is included in CuraGen Corporation's database.Sequences were included as components for assembly when the event ofidentity with another component was at least 95% over 50 bp. Eachassembly represents a gene or portion thereof and includes informationon variants, such as splice forms single nucleotide polymorphisms(SNPs), insertions, deletions and other sequence variations.

[0517] Physical clone: the cDNA fragment derived by the screeningprocedure, covering the entire open reading frame is, as a recombinantDNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library.The recombinant plasmid is inserted into the host and selected by theyeast hybrid diploid generated during the screening procedure by themating of both CuraGen Corporation proprietary yeast strains N106′ andYULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).

[0518] 4. RACE: Techniques based on the polymerase chain reaction suchas rapid amplification of cDNA ends (RACE), were used to isolate orcomplete the predicted sequence of the cDNA of the invention. Usuallymultiple clones were sequenced from one or more human samples to derivethe sequences for fragments. Various human tissue samples from differentdonors were used for the RACE reaction. The sequences derived from theseprocedures were included in the SeqCalling Assembly process described inpreceding paragraphs.

[0519] 5. Exon Linking: The NOVX target sequences identified in thepresent invention were subjected to the exon linking process to confirmthe sequence. PCR primers were designed by starting at the most upstreamsequence available, for the forward primer, and at the most downstreamsequence available for the reverse primer. In each case, the sequence asexamined, walking inward from the respective termini toward the codingsequence, until a suitable sequence that is either unique or highlyselective was encountered, or, in the case of the reverse primer, untilthe stop codon was reached. Such primers were designed based on insilico predictions for the full length cDNA, part (one or more exons) ofthe DNA or protein sequence of the target sequence, or by translatedhomology of the predicted exons to closely related human sequences fromother species. These primers were then employed in PCR amplificationbased on the following pool of human cDNAs: adrenal gland, bone marrow,brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantianigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, fetalliver, fetal lung, heart, kidney, lymphoma—Raji, mammary gland,pancreas, pituitary gland, placenta, prostate, salivary gland, skeletalmuscle, small intestine, spinal cord, spleen, stomach, testis, thyroid,trachea, uterus. Usually the resulting amplicons were gel purified,cloned and sequenced to high redundancy. The PCR product derived fromexon linking was cloned into the pCR2.1 vector from Invitrogen. Theresulting bacterial clone has an insert covering the entire open readingframe cloned into the pCR2.1 vector. The resulting sequences from allclones were assembled with themselves, with other fragments in CuraGenCorporation's database and with public ESTs. Fragments and ESTs wereincluded as components for an assembly when the extent of their identitywith another component of the assembly was at least 95% over 50 bp. Inaddition, sequence traces were evaluated manually and edited forcorrections if appropriate. These procedures provide the sequencereported herein.

[0520] The cDNA coding for the CG122759-02 sequence was cloned byPolymerase Chain Reaction as described using the primers:5′-CTGATGGAGCACCTTGTTCCCAC-3′ SEQ ID NO: 1885′-CTACCTGAGGGTCTTCCAGCTGTCTTTT-3′ SEQ ID NO: 189

[0521] The cDNA coding for the CG125414-02 sequence was cloned byPolymerase Chain Reaction as described using the primers:5′-ATGGAAGGAGACTTCTCGGTGTG-3′ SEQ ID NO: 1905′-CATCACCTTTCACAAGACCACCAC-3′ SEQ ID NO: 191

[0522] 6. Physical Clone: Exons were predicted by homology and theintron/exon boundaries were determined using, standard genetic rules.Exons were further selected and refined by means of similaritydetermination using multiple BLAST (for example, tBlastN, BlastX, andBlastN) searches, and, in some instances, GeneScan and Grail. Expressedsequences from both public and proprietary databases were also addedwhen available to further define and complete the gene sequence. The DNAsequence was then manually corrected for apparent inconsistenciesthereby obtaining the sequences encoding the full-length protein.

[0523] The PCR product derived by exon linking, covering the entire openreading frame, was cloned into the pCR2.1 vector from Invitrogen toprovide clones used for expression and screening purposes.

Example C Quantitative Expression Analysis of Clones in Various Cellsand Tissues

[0524] The quantitative expression of various clones was assessed usingmicrotiter plates containing RNA samples from a variety of normal andpathology-derived cells, cell lines and tissues using real timequantitative PCR (RTQ PCR). RTQ PCR was performed on an AppliedBiosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence DetectionSystem. Various collections of samples are assembled on the plates, andreferred to as Panel 1 (containing normal tissues and cancer celllines). Panel 2 (containing samples derived from tissues from normal andcancer sources), Panel 3 (containing cancer cell lines). Panel 4(containing cells and cell lines from normal tissues and cells relatedto inflammatory conditions), Panel 5D/5I (containing human tissues andcell lines with an emphasis on metabolic diseases),A1_comprehensive_panel (containing normal tissue and samples fromautoinflammatory diseases), Panel CNSD.01 (containing samples fromnormal and diseased brains) and CNS_neurodegeneration_panel (containingsamples from normal and Alzheimer's diseased brains).

[0525] RNA integrity from all samples is controlled for quality byvisual assessment of agarose gel electropherograms using 28S and 18Sribosomal RNA staining, intensity ratio as a guide (2:1 to 2.5:128s:18s) and the absence of low molecular weight RNAs that would beindicative of degradation products. Samples are controlled againstgenomic DNA contamination by RTQ PCR reactions run in the absence ofreverse transcriptase using probe and primer sets designed to amplifyacross the span of a single exon.

[0526] First, the RNA samples were normalized to reference nucleic acidssuch as constitutively expressed genes (for example, β-actin and GAPDH).Normalized RNA (5 μl) was converted to cDNA and analyzed by RTQ-PCRusing One Step RT-PCR Master Mix Reagents (Applied Biosystems: CatalogNo. 4309169) and gene-specific primers according to the manufacturer'sinstructions.

[0527] In other cases, non-normalized RNA samples were converted tosingle strand cDNA (sscDNA) using Superscript II (InvitrogenCorporation: Catalog No. 18064-147) and random hexamers according to themanufacturer's instructions. Reactions containing up to 10 μg of totalRNA were performed in a volume of 20 μl and incubated for 60 minutes at42° C. This reaction can be scaled up to 50 μg of total RNA in a finalvolume of 100 μl. sscDNA samples are then normalized to referencenucleic acids as described previously, using 1× TaqMan® Universal Mastermix (Applied Biosystems: catalog No. 4324020), following, themanufacturer's instructions.

[0528] Probes and primers were designed for each assay according toApplied Biosystems Primer Express Software package (version 1 for AppleComputer's Macintosh Power PC) or a similar algorithm using the targetsequence as input. Default settings were used for reaction conditionsand the following parameters were set before selecting primers: primerconcentration=250 nM, primer melting temperature (Tm) range=58°-60° C.,primer optimal Tm=59° C. maximum primer difference=2° C., probe does nothave 5′G, probe Tm must be 10° C. greater than primer Tm, amplicon size75 bp to 100 bp. The probes and primers selected (see below) weresynthesized by Synthegen (Houston, Tex., USA). Probes were doublepurified by HPLC to remove uncoupled dye and evaluated by massspectroscopy to verify coupling of reporter and quencher dyes to the 5′and 3′ ends of the probe, respectively. Their final concentrations were:forward and reverse primers, 900 nM each, and probe, 200 nM.

[0529] PCR conditions: When working with RNA samples, normalized RNAfrom each tissue and each cell line was spotted in each well of either a96 well or a 384-well PCR plate (Applied Biosystems). PCR cocktailsincluded either a single gene specific probe and primers set, or twomultiplexed probe and primers sets (a set specific for the target cloneand another gene-specific set multiplexed with the target probe). PCRreactions were set up using TaqMan® One-Step RT-PCR Master Mix (AppliedBiosystems, Catalog No. 4313803) following manufacturer's instructions.Reverse transcription was performed at 48° C. for 30 minutes followed byamplification/PCR cycles as follows: 95° C. 10 min, then 40 cycles of95° C. for 15 seconds, 60° C. for 1 minute. Results were recorded as CTvalues (cycle at which a given sample crosses a threshold level offluorescence) using a log scale, with the difference in RNAconcentration between a given sample and the sample with the lowest CTvalue being represented as 2 to the power of delta CT. The percentrelative expression is then obtained by taking the reciprocal of thisRNA difference and multiplying by 100.

[0530] When working with sscDNA samples, normalized sscDNA was used asdescribed previously for RNA samples. PCR reactions containing one ortwo sets of probe and primers were set up as described previously, using1× TaqMan® Universal Master mix (Applied Biosystems: catalog No.4324020), following the manufacturer's instructions. PCR amplificationwas performed as follows: 95° C. 10 min. then 40 cycles of 95° C. for 15seconds, 60° C. for 1 minute. Results were analyzed and processed asdescribed previously.

[0531] Panels 1, 1.1, 1.2, and 1.3D

[0532] The plates for Panels 1, 1.1, 1.2 and 1.3D include 2 controlwells (genomic DNA control and chemistry control) and 94 wellscontaining cDNA from various samples. The samples in these panels arebroken into 2 classes: samples derived from cultured cell lines andsamples derived from primary normal tissues. The cell lines are derivedfrom cancers of the following types: lung cancer, breast cancer,melanoma, colon cancer, prostate cancer, CNS cancer, squamous cellcarcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancerand pancreatic cancer. Cell lines used in these panels are widelyavailable through the American Type Culture Collection (ATCC), arepository for cultured cell lines, and were cultured using theconditions recommended by the ATCC. The normal tissues found on thesepanels are comprised of samples derived from all major organ systemsfrom single adult individuals or fetuses. These samples are derived fromthe following organs: adult skeletal muscle, fetal skeletal muscle,adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetalliver, adult lung, fetal lung, various regions of the brain, the spleen,bone marrow, lymph node, pancreas, salivary gland, pituitary gland,adrenal gland, spinal cord, thymus, stomach, small intestine, colon,bladder, trachea, breast, ovary, uterus, placenta, prostate, testis andadipose.

[0533] In the results for Panels 1, 1.1, 1.2 and 1.3D, the followingabbreviations are used:

[0534] ca.=carcinoma.

[0535] *=established from metastasis,

[0536] met=metastasis.

[0537] s cell var=small cell variant.

[0538] non-s=non-sm=non-small.

[0539] squam=squamous.

[0540] pl. eff=pl effusion=pleural effusion.

[0541] glio=glioma.

[0542] astro=astrocytoma, and

[0543] neuro=neuloblastoma.

[0544] General_screening_panel_v1.4, v1.5 and v1.6

[0545] The plates for Panels 1.4, 1.5, and 1.6 include 2 control wells(genomic DNA control and chemistry control) and 94 wells containing cDNAfrom various samples. The samples in Panels 1.4, 1.5, and 1.6 are brokeninto 2 classes: samples derived from cultured cell lines and samplesderived from primary normal tissues. The cell lines are derived fromcancers of the following types: lung cancer, breast cancer, melanoma,colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma,ovarian cancer, liver cancer, renal cancer, gastric cancer andpancreatic cancer. Cell lines used in Panels 1.4, 1.5, and 1.6 arewidely available through the American Type Culture Collection (ATCC), arepository for cultured cell lines, and were cultured using theconditions recommended by the ATCC. The normal tissues found on Panels1.4, 1.5, and 1.6 are comprised of pools of samples derived from allmajor organ systems from 2 to 5 different adult individuals or fetuses.These samples are derived from the following organs: adult skeletalmuscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney,fetal kidney, adult liver, fetal liver, adult lung, fetal lung, variousregions of the brain, the spleen, bone marrow, lymph node, pancreas,salivary gland, pituitary gland, adrenal gland, spinal cord, thymus,stomach, small intestine, colon, bladder, trachea, breast, ovary,uterus, placenta, prostate, testis and adipose. Abbreviations are asdescribed for Panels 1, 1.1, 1.2, and 1.3D.

[0546] Panels 2D, 2.2, 2.3 and 2.4

[0547] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2control wells and 94 test samples composed of RNA or cDNA isolated fromhuman tissue procured by surgeons working in close cooperation with theNational Cancer Institute's Cooperative Human Tissue Network (CHTN) orthe National Disease Research Initiative (NDRI) or from Ardais orClinomics). The tissues are derived from human malignancies and in caseswhere indicated manly malignant tissues have “matched margins” obtainedfrom noncancerous tissue just adjacent to the tumor. These are termednormal adjacent tissues and are denoted “NAT” in the results below. Thetumor tissue and the “matched margins” are evaluated by two independentpathologists (the surgical pathologists and again by a pathologist atNDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues withoutmalignancy (normal tissues) were also obtained from Ardais or Clinomics.This analysis provides a gross histopathological assessment of tumordifferentiation grade. Moreover, most samples include the originalsurgical pathology report that provides information regarding theclinical stage of the patient. These matched margins are taken from thetissue surrounding (i.e. immediately proximal) to the zone of surgery(designated “NAT”, for normal adjacent tissue, in Table RR). Inaddition, RNA and cDNA samples were obtained from various human tissuesderived from autopsies performed on elderly people or sudden deathvictims (accidents, etc.). These tissues were ascertained to be free ofdisease and were purchased from various commercial sources such asClontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.

[0548] HASS Panel v 1.0

[0549] The HASS panel v 1.0 plates are comprised of 93 cDNA samples andtwo controls. Specifically, 81 of these samples are derived fromcultured human cancer cell lines that had been subjected to serumstarvation, acidosis and anoxia for different time periods as well ascontrols for these treatments, 3 samples of human primary cells, 9samples of malignant brain cancer (4 medulloblastomas and 5glioblastomas) and 2 controls. The human cancer cell lines are obtainedfrom ATCC (American Type Culture Collection) and fall into the followingtissue groups: breast cancer, prostate cancer, bladder carcinomas,pancreatic cancers and CNS cancer cell lines. These cancer cells are allcultured under standard recommended conditions. The treatments used(serum starvation, acidosis and anoxia) have been previously publishedin the scientific literature. The primary human cells were obtained fromClonetics (Walkersville, Md.) and were grown in the media and conditionsrecommended by Clonetics. The malignant brain cancer samples areobtained as part of a collaboration (Henry Ford Cancer Center) and areevaluated by a pathologist prior to CuraGen receiving the samples. RNAwas prepared from these samples using the standard procedures. Thegenomic and chemistry control wells have been described previously.

[0550] ARDAIS Panel v 1.0

[0551] The plates for ARDAIS panel v 1.0 generally include 2 controlwells and 22 test samples composed of RNA isolated from human tissueprocured by surgeons workings in close cooperation with ArdaisCorporation. The tissues are derived from human lung malignancies (lungadenocarcinoma or lung squamous cell carcinoma) and in cases whereindicated many malignant samples have “matched margins” obtained fromnoncancerous lung tissue just adjacent to the tumor. These matchedmargins are taken from the tissue surrounding (i.e. immediatelyproximal) to the zone of surgery (designated “NAT”, for normal adjacenttissue) in the results below. The tumor tissue and the “matched margins”are evaluated by independent pathologists (the surgical pathologists andagain by a pathologist at Ardais). Unmatched malignant and non-malignantRNA samples from lungs were also obtained from Ardais. Additionalinformation from Ardais provides a gross histopathological assessment oftumor differentiation grade and stage. Moreover, most samples includethe original surgical pathology, report that provides informationregarding the clinical state of the patient.

[0552] Panel 3D, 3.1 and 3.2

[0553] The plates of Panel 3D, 3.1, and 3.2 are comprised of 94 cDNAsamples and two control samples. Specifically, 92 of these samples arederived from cultured human cancer cell lines 2 samples of human primarycerebellar tissue and 2 controls. The human cell lines are generallyobtained from ATCC (American Type Culture Collection), NCI or the Germantumor cell bank and fall into the following tissue groups: Squamous cellcarcinoma of the tongue, breast cancer, prostate cancer, melanoma,epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers,kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric,colon, lung and CNS cancer cell lines. In addition, there are twoindependent samples of cerebellum. These cells are all cultured understandard recommended conditions and RNA extracted using the standardprocedures. The cell lines in panel 3D, 3.1, 3.2, 1, 1.1, 1.2, 1.3D,1.4, 1.5, and 1.6 are of the most common cell lines used in thescientific literature.

[0554] Panels 4D, 4R, and 4.1D

[0555] Panel 4 includes samples on a 96 well plate (2 control wells, 94test samples) composed of RNA (Panel 4R) or cDNA (Panels 4D/4.1D)isolated from various human cell lines or tissues related toinflammatory conditions. Total RNA from control normal tissues such ascolon and lung (Stratagene, La Jolla, Calif.) and thymus and kidney(Clontech) was employed. Total RNA from liver tissue from cirrhosispatients and kidney from lupus patients was obtained from BioChain(Biochain Institute, Inc., Hayward, Calif.). Intestinal tissue for RNApreparation from patients diagnosed as having Crohn's disease andulcerative colitis was obtained from the National Disease ResearchInterchange (NDRI) (Philadelphia, Pa.).

[0556] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary arterysmooth muscle cells, small airway epithelium, bronchial epithelium,microvascular dermal endothelial cells, microvascular lung endothelialcells, human pulmonary aortic endothelial cells, human umbilical veinendothelial cells were all purchased from Clonetics (Walkersville, Md.)and grown in the media supplied for these cell types by Clonetics. Theseprimary cell types were activated with various cytokines or combinationsof cytokines for 6 and/or 12-14 hours, as indicated. The followingcytokines were used: IL-1 beta at approximately 1-5 ng/ml, TNF alpha atapproximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml, IL-13 atapproximately 5-10 ng/ml. Endothelial cells were sometimes starved forvarious times by culture in the basal media from Clonetics with 0.1%serum.

[0557] Mononuclear cells were prepared from blood of employees atCuraGen Corporation, using Ficoll. LAK cells ere prepared from thesecells by culture in DMEM 5% FCS (Hyclone). 100 μM non essential aminoacids (Gibco/Life Technologies, Rockville, Md.). 1 mM sodium pyruvate(Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) andInterleukin 2 for 4-6 days. Cells were then either activated with 10-20ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases,mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone),100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco),mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) with PHA(phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml.Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR(mixed lymphocyte reaction) samples were obtained by taking blood fromtwo donors, isolating the mononuclear cells using Ficoll and mixing theisolated mononuclear cells 1:1 at a final concentration of approximately2×10⁶ cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential aminoacids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10⁻⁵M)(Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples takenat various time points ranging from 1-7 days for RNA preparation.

[0558] Monocytes were isolated from mononuclear cells using CD14Miltenyi Beads, +ve VS selection columns and a Vario Magnet according tothe manufacturer's instructions. Monocytes were differentiated intodendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone,Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodiumpyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes(Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages wereprepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone),100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco),mercaptoethanol 5.5×10⁻⁵M (Gibco), 10 mM Hepes (Gibco) and 10% AB HumanSerum or MCSF at approximately 50 ng/ml. Monocytes, macrophages anddendritic cells were stimulated for 6 and 12-14 hours withlipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were alsostimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/mlfor 6 and 12-14 hours.

[0559] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolatedfrom mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positiveVS selection columns and a Vario Magnet according to the manufacturer'sinstructions. CD45RA and CD45RO CD4 lymphocytes were isolated bydepleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8,CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beadswere then used to isolate the CD45RO CD4 lymphocytes with the remainingcells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 μM non essentialamino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) and plated at 10⁶ cells/mlonto Falcon 6 well tissue culture plates that had been coated overnightwith 0.5 μg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC)in PBS. After 6 and 24 hours, the cells were harvested for RNApreparation. To prepare chronically activated CD8 lymphocytes, weactivated the isolated CD8 lymphocytes for 4 days on anti-CD28 andanti-CD3 coated plates and then harvested the cells and expanded them inDMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mMsodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mMHepes (Gibco) and IL-2. The expanded CD8 cells were then activated againwith plate bound anti-CD3 and anti-CD28 for 4 days and expanded asbefore. RNA was isolated 6 and 24 hours after the second activation andafter 4 days of the second expansion culture. The isolated NK cells werecultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids(Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M(Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA wasprepared.

[0560] To obtain B cells, tonsils were procured from NDRI. The tonsilwas cut up with sterile dissecting scissors and then passed through asieve. Tonsil cells were then spun down and resupended at 10⁶ cells/mlin DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mMsodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mMHepes (Gibco). To activate the cells, we used PWM at 5 μg/ml oranti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml.Cells were harvested for RNA preparation at 24, 48 and 72 hours.

[0561] To prepare the primary and secondary Th1/Th2 and Tr1 cells,six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28(Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS.Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.)were cultured at 10⁵-10⁶ cells/ml in DMEM 5% FCS (Hyclone), 100 μM nonessential amino acids (Gibco), 1 mM sodium pyruvate (Gibco),mercaptoethanol 5.5×10⁻⁵M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct toTh1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used todirect to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5days, the activated Th1, Th2 and Tr1 lymphocytes were washed once inDMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 μM nonessential amino acids (Gibco), 1 mM sodium pyruvate (Gibco),mercaptoethanol 5.5×10⁻⁵M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1ng/ml). Following this, the activated Th1, Th2 and Tr1 lymphocytes werere-stimulated for 5 days with anti-CD28/OKT3 and cytokines as describedabove, but with the addition of anti-CD95L (1 μg/ml) to preventapoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washedand then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2lymphocytes were maintained in this way for a maximum of three cycles.RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and24 hours following the second and third activations with plate boundanti-CD3 and anti-CD28 mAbs and 4 days into the second and thirdexpansion cultures in Interleukin 2.

[0562] The following leukocyte cells lines were obtained from the ATCC:Ramos, EOL-1, KU-812. EOL cells were further differentiated by culturein 0.1 mM dbcAMP at 5×10⁵ cells/ml for 8 days, changing the media every3 days and adjusting the cell concentration to 5×10⁵ cells/ml. For theculture of these cells, we used DMEM or RPMI (as recommended by theATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential aminoacids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M(Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cellsor cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumorline NCI-H292 were also obtained from the ATCC. Both were cultured inDMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mMsodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mMHepes (Gibco). CCD1106 cells were activated for 6 and 14 hours withapproximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292cells were activated for 6 and 14 hours with the following cytokines: 5ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

[0563] For these cell lines and blood cells, RNA was prepared by lysingapproximately 10⁷ cells/ml using Trizol (Gibco BRL). Briefly, 1/10volume of bromochloropropane (Molecular Research Corporation) was addedto the RNA sample, vortexed and after 10 minutes at room temperature,the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueousphase was removed and placed in a 15 ml Falcon Tube. An equal volume ofisopropanol was added and left at −20° C. overnight. The precipitatedRNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor andwashed in 70% ethanol. The pellet was redissolved in 300 μl ofRNAse-free water and 35 μl buffer (Promega) 5 μl DTT. 7 μl RNAsin and 8μl DNAse were added. The tube was incubated at 37° C. for 30 minutes toremove contaminating genomic DNA, extracted once with phenol chloroformand re-precipitated with 1/10 volume of 3M sodium acetate and 2 volumesof 100% ethanol. The RNA was spun down and placed in RNAse free water.RNA was stored at −80° C.

[0564] A1_comprehensive panel_v1.0

[0565] The plates for A1_comprehensive panel_v1.0 include two controlwells and 89 test samples comprised of cDNA isolated from surgical andpostmortem human tissues obtained from the Backus Hospital and Clinomics(Frederick, Md.). Total RNA was extracted from tissue samples from theBackus Hospital in the Facility at CuraGen. Total RNA from other tissueswas obtained from Clinomics.

[0566] Joint tissues including synovial fluid, synovium, bone andcartilage were obtained from patients undergoing total knee or hipreplacement surgery at the Backus Hospital. Tissue samples wereimmediately snap frozen in liquid nitrogen to ensure that isolated RNAwas of optimal quality and not degraded. Additional samples ofosteoarthritis and rheumatoid arthritis joint tissues were obtained fromClinomics. Normal control tissues were supplied by Clinomics and wereobtained during autopsy of trauma victims.

[0567] Surgical specimens of psoriatic tissues and adjacent matchedtissues were provided as total RNA by Clinomics. Two male and two femalepatients were selected between the ages of 25 and 47. None of thepatients were taking prescription drugs at the time samples wereisolated.

[0568] Surgical specimens of diseased colon from patients withulcerative colitis and Crohns disease and adjacent matched tissues wereobtained from Clinomics. Bowel tissue from three female and three maleCrohn's patients between the ages of 41-69 were used. Two patients werenot on prescription medication while the others were takingdexamethasone phenobarbital, or tylenol. Ulcerative colitis tissue wasfrom three male and four female patients. Four of the patients weretaking lebvid and two were on phenobarbital.

[0569] Total RNA from post mortem lung tissue from trauma victims withno disease or with emphysema, asthma or COPD as purchased fromClinomics. Emphysema patients ranged in age from 40-70 and all weresmokers, this age range was chosen to focus on patients withcigarette-linked emphysema and to avoid those patients with alpha-1anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, andexcluded smokers to prevent those patients that could also have COPD.COPD patients ranged in age from 35-80 and included both smokers andnon-smokers. Most patients were taking corticosteroids, andbronchodilators.

[0570] In the labels employed to identify tissues in theA1_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0571] AI=Autoimmunity

[0572] Syn=Synovial

[0573] Normal=No apparent disease

[0574] Rep22/Rep20=individual patients

[0575] RA=Rheumatoid arthritis

[0576] Backus=From Backus Hospital

[0577] OA=Osteoarthritis

[0578] (SS) (BA) (MF)=Individual patients

[0579] Adj=Adjacent tissue

[0580] Match control=adjacent tissues

[0581] -M=Male

[0582] -F=Female

[0583] COPD=Chronic obstructive pulmonary disease

[0584] Panels 5D and 5I

[0585] The plates for Panel 5D and 5I include two control wells and avariety of cDNAs isolated from human tissues and cell lines with anemphasis on metabolic diseases. Metabolic tissues were obtained frompatients enrolled in the Gestational Diabetes study. Cells were obtainedduring different stages in the differentiation of adipocytes from humanmesenchymal stem cells. Human pancreatic islets were also obtained.

[0586] In the Gestational Diabetes study subjects are young (18-40years), otherwise health women with and without gestational diabetesundergoing routine (elective) Caesareyan section. After delivery of theinfant, when the surgical incisions were being repaired/closed, theobstetrician removed a small sample (<1 cc) of the exposed metabolictissues during the closure of each surgical level. The biopsy materialwas rinsed in sterile saline, blotted and fast frozen within 5 minutesfrom the time of removal. The tissue was then flash frozen in liquidnitrogen and stored, individually, in sterile screw-top tubes and kepton dry ice for shipment to or to be picked up by CuraGen. The metabolictissues of interest include uterine wall (smooth muscle), visceraladipose, skeletal muscle (rectus) and subcutaneous adipose. Patientdescriptions are as follows:

[0587] Patient 2: Diabetic Hispanic, overweight, not on insulin

[0588] Patient 7-9: Nondiabetic Caucasian and obese (BMI>30)

[0589] Patient 10: Diabetic Hispanic, overweight, on insulin

[0590] Patient 11: Nondiabetic African American and overweight

[0591] Patient 12: Diabetic Hispanic on insulin

[0592] Adiocyte differentiation was induced in donor progenitor cellsobtained from Osirus (a division of Clonetics/BioWhittaker) intriplicate, except for Donor 3U which had only two replicates.Scientists at Clonetics isolated, grew and differentiated humanmesenchymal stem cells (HuMSCs) for CuraGen based on the publishedprotocol found in Mark F. Pittenger, et al., Multilineage Potential ofAdult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147.Clonetics provided Trizol lysates or frozen pellets suitable for mRNAisolation and ds cDNA production. A general description of each donor isas follows:

[0593] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0594] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0595] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0596] Human cell lines were generally obtained from ATCC (American TypeCulture Collection), NCI or the German tumor cell bank and fall into thefollowing tissue groups: kidney proximal convoluted tubule, uterinesmooth muscle cells, small intestine, liver HepG2 cancer cells, heartprimary stromal cells, and adrenal cortical adenoma cells. These cellsare all cultured under standard recommended conditions and RNA extractedusing the standard procedures. All samples were processed at CuraGen toproduce single stranded cDNA.

[0597] Panel 51 contains all samples previously described with theaddition of pancreatic islets from a 58 year old female patient obtainedfrom the Diabetes Research Institute at the University of Miami Schoolof Medicine. Islet tissue was processed to total RNA at an outsidesource and delivered to CuraGen for addition to panel 51.

[0598] In the labels employed to identify tissues in the 5D and 5Ipanels, the following abbreviations are used:

[0599] GO Adipose=Greater Omentum Adipose

[0600] SK=Skeletal Muscle

[0601] UT=Uterus

[0602] PL=Placenta

[0603] AD=Adipose Differentiated

[0604] AM=Adipose Midway Differentiated

[0605] U=Undifferentiated Stem Cells

[0606] Panel CNSD.01

[0607] The plates for Panel CNSD.01 include two control wells and 94test samples comprised of cDNA isolated from postmortem human braintissue obtained from the Harvard Brain Tissue Resource Center. Brainsare removed from calvaria of donors between 4 and 24 hours after death,sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogenvapor. All brains are sectioned and examined by neuropathologists toconfirm diagnoses with clear associated neuropathology.

[0608] Disease diagnoses are taken from patient records. The panelcontains two brains from each of the following diagnoses: Alzheimer'sdisease, Parkinson's disease, Huntington's disease, ProgressiveSupernuclear Palsy, Depression, and “Normal controls”. Within each ofthese brains, the following regions are represented: cingulate gyrus,temporal pole, globus palladus, substantia nigra, Brodman Area 4(primary motor strip), Brodman Area 7 (parietal cortex), Brodman Area 9(prefrontal cortex), and Brodman area 17 (occipital cortex). Not allbrain regions are represented in all cases; e.g., Huntington's diseaseis characterized in part by neurodegeneration in the globus palladus,thus this region is impossible to obtain from confirmed Huntington'scases. Likewise Parkinson's disease is characterized by degeneration ofthe substantia nigra making this region more difficult to obtain. Normalcontrol brains were examined for neuropathology and found to be free ofany pathology consistent with neurodegeneration.

[0609] In the labels employed to identify tissues in the CNS panel, thefollowing abbreviations are used:

[0610] PSP=Progressive supranuclear palsy

[0611] Sub Nigra=Substantia nigra

[0612] Glob Palladus=Globus palladus

[0613] Temp Pole=Temporal pole

[0614] Cing Gyr=Cingulate gyrus

[0615] BA 4 =Brodman Area 4

[0616] Panel CNS_Neurodegeneration_V1.0

[0617] The plates for Panel CNS_Neurodegeneration_V1.0 include tocontrol wells and 47 test samples comprised of cDNA isolated frompostmortem human brain tissue obtained from the Harvard Brain TissueResource Center (McLean Hospital) and the Human Brain and Spinal FluidResource Center (VA Greater Los Angeles Healthcare System). Brains areremoved from calvaria of donors between 4 and 24 hours after death,sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogenvapor. All brains are sectioned and examined by neuropathologists toconfirm diagnoses with clear associated neuropathology.

[0618] Disease diagnoses are taken from patient records. The panelcontains six brains from Alzheimer's disease (AD) patients, and eightbrains from “Normal controls” who showed no evidence of dementia priorto death. The eight normal control brains are divided into twocategories: Controls with no dementia and no Alzheimer's like pathology(Controls) and controls with no dementia but evidence of severeAlzheimer's like pathology, (specifically senile plaque load rated aslevel 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senileplaque load). Within each of these brains, the following regions arerepresented: hippocampus, temporal cortex (Brodman Area 21), parietalcortex (Brodman area 7), and occipital cortex (Brodman area 17). Theseregions were chosen to encompass all levels of neurodegeneration in AD.The hippocampus is a region of early and severe neuronal loss in AD; thetemporal cortex is known to show neurodegeneration in AD after thehippocampus; the parietal cortex shows moderate neuronal death in thelate stages of the disease; the occipital cortex is spared in AD andtherefore acts as a “control” region within AD patients. Not all brainregions are represented in all cases.

[0619] In the labels employed to identify tissues in theCNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0620] AD=Alzheimer's disease brain: patient was demented and showedAD-like pathology upon autopsy

[0621] Control=Control brains: patient not demented, showing noneuropathology

[0622] Control (Path)=Control brains: pateint not demented but showingsever AD-like pathology

[0623] SupTemporal Ctx=Superior Temporal Cortex

[0624] Inf Temporal Ctx=Inferior Temporal Cortex

[0625] A. CG102071-01: MAP KINASE PHOSPHATASE-LIKE PROTEIN

[0626] Expression of full length physical clone CG102071-01 as assessedusing the primer-probe set Ag6814, described in Table AA. TABLE AA ProbeName Ag6814 Primers Sequences Length Start Position SEQ ID No Forward5′-tgatggcaaaggaactggat-3′ 20 339 89 ProbeTET-5′-ccataccccattgaaatcgtgcca-3′-TAMRA 24 368 90 Reverse5′-aatcttggggtcacaggctt-3′ 20 420 91

[0627] CNS_neurodegeneration_v1.0 Summary: Ag6814 Expression of thisgene is low/undetectable in all samples on this panel (CTs>35).

[0628] General_screening_panel_v1.6 Summary: Ag6814 Expression of thisgene is low/undetectable in all samples on this panel (CTs>35).

[0629] Panel 4.1D Summary: Ag6814 Expression of this gene islow/undetectable in all samples on this panel (CTs>35). (Data notshown.)

[0630] B. CG112767-01 and CG112767-02: Cyclin

[0631] Expression of gene CG112767-01 and full length physical cloneCG112767-02 was assessed using the primer-probe set Ag4461, described inTable BA. Results of the RTQ-PCR runs are shown in Tables BB, BC, BD andBE. Please note that CG112767-02 represents a full-length physical cloneof the CG112767-01 gene, validating the prediction of the gene sequence.TABLE BA Probe Name Ag4461 Start SEQ ID Primers Sequences LengthPosition No Forward 5′-ggtttgacagatctggaatgtg-3′ 22 27 92 ProbeTET-5′-ctattcctccgcagtctggcctgtct-3′-TAMRA 26 54 93 Reverse5′-gctggcaaagaagacagaaag-3′ 21 81 94

[0632] TABLE BB CNS_neurodcgeneration_v1.0 Rel. Exp. (%) Rel. Exp. (%)Ag4461, Ag4461, Tissue Name Run 224621596 Tissue Name Run 224621596 AD 1Hippo 54.7 Control (Path) 3 Temporal Ctx 12.9 AD 2 Hippo 3.7 Control(Path) 4 Temporal Ctx 8.8 AD 3 Hippo 8.6 AD 1 Occipital Ctx 11.3 AD 4Hippo 8.1 AD 2 Occipital Ctx (Missing) 0.0 AD 5 hippo 52.9 AD 3Occipital Ctx 35.4 AD 6 Hippo 100.0 AD 4 Occipital Ctx 7.7 Control 2Hippo 10.7 AD 5 Occipital Ctx 9.2 Control 4 Hippo 0.0 AD 6 Occipital Ctx27.9 Control (Path) 3 Hippo 28.3 Control 1 Occipital Ctx 0.0 AD 1Temporal Ctx 7.6 Control 2 Occipital Ctx 15.9 AD 2 Temporal Ctx 19.5Control 3 Occipital Ctx 0.0 AD 3 Temporal Ctx 0.0 Control 4 OccipitalCtx 0.0 AD 4 Temporal Ctx 0.0 Control (Path) 1 Occipital Ctx 16.7 AD 5Inf Temporal Ctx 26.4 Control (Path) 2 Occipital Ctx 0.0 AD 5 SupTemporal Ctx 45.4 Control (Path) 3 Occipital Ctx 0.0 AD 6 Inf TemporalCtx 93.3 Control (Path) 4 Occipital Ctx 18.2 AD 6 Sup Temporal Ctx 13.5Control 1 Parietal Ctx 15.3 Control 1 Temporal Ctx 9.0 Control 2Parietal Ctx 13.4 Control 2 Temporal Ctx 0.0 Control 3 Parietal Ctx 8.7Control 3 Temporal Ctx 0.0 Control (Path) 1 Parietal Ctx 5.4 Control 4Temporal Ctx 0.0 Control (Path) 2 Parietal Ctx 13.3 Control (Path) 1Temporal Ctx 15.9 Control (Path) 3 Parietal Ctx 0.0 Control (Path) 2Temporal Ctx 46.7 Control (Path) 4 Parietal Ctx 18.4

[0633] TABLE BC General_screening_panel_v1.4 Rel. Exp. (%) Rel. Exp. (%)Ag4461, Ag4461, Tissue Name Run 222523507 Tissue Name Run 222523507Adipose 0.6 Renal ca. TK-10 7.2 Melanoma* Hs688(A).T 0.1 Bladder 1.7Melanoma* Hs688(B).T 0.0 Gastric ca. (liver met.) NCI-N87 7.2 Melanoma*M14 2.9 Gastric ca. KATO III 0.0 Melanoma* LOXIMVI 1.0 Colon ca. SW-9480.7 Melanoma* SK-MEL-5 5.5 Colon ca. SW480 12.3 Squamous cell carcinomaSCC-4 1.1 Colon ca.* (SW480 met) SW620 12.4 Testis Pool 8.2 Colon ca.HT29 5.3 Prostate ca.* (bone met) PC-3 27.9 Colon ca. HCT-116 3.8Prostate Pool 0.6 Colon ca. CaCo-2 19.3 Placenta 1.0 Colon cancer tissue1.9 Uterus Pool 0.0 Colon ca. SW1116 3.3 Ovarian ca. OVCAR-3 13.7 Colonca. Colo-205 0.0 Ovarian ca. SK-OV-3 23.0 Colon ca. SW-48 0.0 Ovarianca. OVCAR-4 34.9 Colon Pool 0.4 Ovarian ca. OVCAR-5 23.8 Small IntestinePool 1.8 Ovarian ca. IGROV-1 2.3 Stomach Pool 2.1 Ovarian ca. OVCAR-89.1 Bone Marrow Pool 1.3 Ovary 2.7 Fetal Heart 9.3 Breast ca. MCF-7 6.0Heart Pool 0.0 Breast ca. MDA-MB-231 28.3 Lymph Node Pool 4.0 Breast ca.BT 549 1.1 Fetal Skeletal Muscle 3.3 Breast ca. T47D 27.0 SkeletalMuscle Pool 0.0 Breast ca. MDA-N 2.7 Spleen Pool 3.6 Breast Pool 2.0Thymus Pool 2.4 Trachea 1.2 CNS cancer (glio/astro) U87-MG 0.0 Lung 2.1CNS cancer (glio/astro) U-118-MG 0.6 Fetal Lung 34.6 CNS cancer (neuro:met) SK-N-AS 11.9 Lung ca. NCI-N417 0.0 CNS cancer (astro) SF-539 2.4Lung ca. LX-1 18.7 CNS cancer (astro) SNB-75 11.7 Lung ca. NCI-H146 2.4CNS cancer (glio) SNB-19 2.3 Lung ca. SHP-77 15.1 CNS cancer (glio)SF-295 30.1 Lung ca. A549 16.5 Brain (Amygdala) Pool 0.0 Lung ca.NCI-H526 0.0 Brain (cerebellum) 100.0 Lung ca. NCI-H23 1.5 Brain (fetal)6.9 Lung ca. NCI-H460 20.4 Brain (Hippocampus) Pool 0.0 Lung ca. HOP-629.6 Cerebral Cortex Pool 0.3 Lung ca. NCI-H522 2.4 Brain (Substantianigra) Pool 1.7 Liver 0.0 Brain (Thalamus) Pool 1.2 Fetal Liver 1.7Brain (whole) 9.4 Liver ca. HepG2 2.6 Spinal Cord Pool 1.0 Kidney Pool0.8 Adrenal Gland 5.6 Fetal Kidney 13.2 Pituitary gland Pool 0.3 Renalca. 786-0 2.5 Salivary Gland 4.4 Renal ca. A498 6.7 Thyroid (female) 0.5Renal ca. ACHN 6.0 Pancreatic ca. CAPAN2 16.6 Renal ca. UO-31 7.1Pancreas Pool 2.3

[0634] TABLE BD Panel 4.1D Rel. Rel. Exp. (%) Exp. (%) Ag4461, Rel. Exp.(%) Ag4461, Rel. Exp. (%) Run Ag4461, Run Run Ag4461, Run Tissue Name44579104 195509495 Tissue Name 44579104 195509495 Secondary Th1 act 0.00.0 HUVEC IL-1beta 10.4 4.0 Secondary Th2 act 1.3 1.1 HUVEC IFN 7.3 9.5gamma Secondary Tr1 act 0.0 0.0 HUVEC TNF 5.5 3.2 alpha + IFN gammaSecondary Th1 rest 0.0 0.0 HUVEC TNF 2.2 4.8 alpha + IL4 Secondary Th2rest 0.0 0.0 HUVEC IL-11 20.3 5.8 Secondary Tr1 rest 1.4 0.0 LungMicrovascular 37.9 9.3 EC none Primary Th1 act 0.0 0.0 LungMicrovascular 8.4 6.3 EC TNFalpha + IL- 1beta Primary Th2 act 0.0 0.0Microvascular 18.4 8.6 Dermal EC none Primary Tr1 act 0.0 0.0Microsvasular 1.2 0.8 Dermal EC TNFalpha + IL- 1beta Primary Th1 rest0.0 0.0 Bronchial 19.6 8.0 epithelium TNFalpha + IL1beta Primary Th2rest 0.3 0.0 Small airway 3.3 2.3 epithelium none Primary Tr1 rest 0.00.0 Small airway 17.0 4.8 epithelium TNFalpha + IL- 1beta CD45RA CD4 1.21.9 Coronery artery 1.5 1.0 lymphocyte act SMC rest CD45RO CD4 0.0 0.0Coronery artery 2.1 0.0 lymphocyte act SMC TNFalpha + IL-1beta CD8lymphocyte act 0.0 1.8 Astrocytes rest 10.9 2.3 Secondary CD8 0.0 0.0Astrocytes 5.0 7.3 lymphocyte rest TNFalpha + IL- 1beta Secondary CD80.0 0.0 KU-812 (Basophil) 0.0 0.0 lymphocyte act rest CD4 lymphocyte 1.30.9 KU-812 (Basophil) 0.0 0.0 none PMA/ionomycin 2ry 2.5 0.5 CCD110627.9 11.4 Th1/Th2/Tr1_anti- (Keratinocytes) CD95 CH11 none LAK cellsrest 1.2 0.0 CCD1106 (Keratinocytes) 18.4 3.4 TNFalpha + IL- 1 beta LAKcells IL-2 4.5 3.3 Liver cirrhosis 1.2 0.0 LAK cells IL-2 + IL- 5.3 0.9NCI-H292 none 12.2 7.8 12 LAK cells IL- 6.0 0.0 NCI-H292 IL-4 10.2 19.52 + IFN gamma LAK cells IL-2 + IL- 3.5 2.1 NCI-H292 IL-9 20.7 6.8 18 LAKcells 3.9 0.0 NCI-H292 IL-13 7.2 4.1 PMA/ionomycin NK Cells IL-2 rest33.9 26.8 NCI-H292 IFN 14.3 0.0 gamma Two Way MLR 3 6.0 6.1 HPAEC none14.6 8.4 day Two Way MLR 5 2.5 0.0 HPAEC 5.7 8.1 day TNF alpha + IL-1beta Two Way MLR 7 0.0 0.0 Lung fibroblast 4.9 1.0 day none PBMC rest0.0 0.0 Lung fibroblast 2.7 0.0 TNF alpha + IL-1 beta PBMC PWM 0.0 0.0Lung fibroblast IL-4 1.2 0.0 PBMC PHA-L 1.7 0.0 Lung fibroblast IL- 2.60.9 9 Ramos (B cell) none 0.0 0.0 Lung fibroblast IL- 3.8 1.1 13 Ramos(B cell) 0.0 0.0 Lung fibroblast IFN 1.3 0.9 ionomycin gamma Blymphocytes 0.0 0.0 Dermal fibroblast 0.0 0.0 PWM CCD1070 rest Blymphocytes 0.0 0.0 Dermal fibroblast 2.7 0.0 CD40L and IL-4 CCD1070 TNFalpha EOL-1 dbcAMP 0.0 0.0 Dermal fibroblast 1.2 1.8 CCD1070 IL-1 betaEOL-1 dbcAMP 0.0 0.0 Dermal fibroblast 0.0 0.0 PMA/ionomycin IFN gammaDendritic cells none 0.0 0.8 Dermal fibroblast 0.0 4.6 IL-4 Dendriticcells LPS 0.0 0.9 Dermal Fibroblasts 0.0 3.8 rest Dendritic cells anti-0.0 0.0 Neutrophils 1.3 5.6 CD40 TNFa + LPS Monocytes rest 0.0 0.0Neutrophils rest 100.0 57.4 Monocytes LPS 0.0 0.0 Colon 2.6 1.1Macrophages rest 0.0 0.9 Lung 5.0 16.8 Macrophages LPS 0.0 0.0 Thymus19.1 25.7 HUVEC none 8.7 5.2 Kidney 14.9 100.0 HUVEC starved 29.3 12.9

[0635] TABLE BE general oncology screening panel_v_2.4 Rel. Exp. Rel.Exp. (%) Ag4461, (%) Ag4461, Run Run Tissue Name 268672303 Tissue Name268672303 Colon cancer 1 4.0 Bladder NAT 2 0.0 Colon NAT 1 7.0 BladderNAT 3 0.0 Colon cancer 2 7.0 Bladder NAT 4 0.0 Colon NAT 2 5.7 Prostate7.6 adenocarcinoma 1 Colon cancer 3 5.6 Prostate 0.0 adenocarcinoma 2Colon NAT 3 8.0 Prostate 0.0 adenocarcinoma 3 Colon malignant 4.4Prostate 12.9 cancer 4 adenocarcinoma 4 Colon NAT 4 16.2 Prostate NAT 51.7 Lung cancer 1 30.4 Prostate 0.0 adenocarcinoma 6 Lung NAT 1 11.4Prostate 1.1 adenocarcinoma 7 Lung cancer 2 34.9 Prostate 0.0adenocarcinoma 8 Lung NAT 2 15.1 Prostate 4.6 adenocarcinoma 9 Squamouscell 16.6 Prostate NAT 10 1.8 carcinoma 3 Lung NAT 3 0.0 Kidney cancer 123.5 Metastatic 17.3 Kidney NAT 1 4.0 melanoma 1 Melanoma 2 0.0 Kidneycancer 2 100.0 Melanoma 3 0.0 Kidney NAT 2 38.7 Metastatic 32.3 Kidneycancer 3 2.6 melanoma 4 Metastatic 34.6 Kidney NAT 3 7.7 melanoma 5Bladder cancer 1 0.0 Kidney cancer 4 0.0 Bladder NAT 1 0.0 Kidney NAT 40.0 Bladder cancer 2 4.6

[0636] CNS_neurodegeneration_v1.0 Summary: Ag4461 This panel does notshow differential expression of this gene in Alzheimer's disease.However, this expression profile confirms the presence of this gene inthe brain. Please see Panel 1.4 for discussion of this gene in thecentral nervous system.

[0637] General_screening_panel_v1.4 Summary: Ag4461 Highest expressionof this gene is seen in the cerebellum (CT=28.7). This expression in thecerebellum suggests that the protein encoded by this gene may be auseful and specific target of drugs for the treatment of CNS disordersthat have this brain region as the site of pathology, such as autism andthe ataxias.

[0638] This gene is also widely expressed in this panel in the samplesderived from cancer cell lines, with moderate to low expression seen inbrain, colon, gastric, lung, breast, ovarian, and melanoma cancer celllines. This expression profile suggests a role for this gene product incell survival and proliferation. Modulation of this gene product may beuseful in the treatment of cancer.

[0639] Among tissues with metabolic function, this gene is expressed atlow but significant levels in adrenal gland, pancreas, and fetalskeletal muscle, heart, and liver. This expression among these tissuessuggests that this gene product may play a role in normal neuroendocrineand metabolic function and that disregulated expression of this gene maycontribute to neuroendocrine disorders or metabolic diseases, such asobesity and diabetes.

[0640] In addition, this gene is expressed at much higher levels infetal lung (CT=30) when compared to expression in the adult counterpart(CT=34). Thus, expression of this gene may be used to differentiatebetween the fetal and adult source of this tissue.

[0641] Panel 4.1D Summary: Ag4461 Two experiments with the same probeand primer set produce results that are in reasonable agreement, withhighest expression in resting neutrophils and kidney (CTs=31). Thus,expression of this gene could be used to differentiate between thesesamples and other samples on this panel and specificaly between restingand activated neutrophils.

[0642] general oncology screening panel_v_(—)2.4 Summary: Ag4461 Highestexpression is seen in kidney cancer (CT=32.5). Low but significantlevels of expression are also seen in two samples derived frommetastatic melanoma. Thus, modulation of the expression or function ofthis gene could be effective in the treatment of kidney cancer andmetastatic melanoma.

[0643] C. CG112776-01: Gag-like

[0644] Expression of gene CG112776-01 was assessed using theprimer-probe set Ag4462, described in Table CA. Results of the RTQ-PCRruns are shown in Tables CB, CC, CD and CE. TABLE CA Probe Name Ag4462Start SEQ ID Primers Sequences Length Position No Forward5′-gggttgaggaagactaggagaa-3′ 22 1021 95 ProbeTET-5′-actcaatgctatccaccattacccag-3′-TAMRA 26 1055 96 Reverse5′-ctgagggattttcttcttttcc-3′ 22 1081 97

[0645] TABLE CB CNS neurodegeneration v1.0 Rel. Exp. (%) Rel. Exp. (%)Ag4462, Ag4462, Tissue Name Run 224621597 Tissue Name Run 224621597 AD 1Hippo 5.1 Control (Path) 3 14.0 Temporal Ctx AD 2 Hippo 39.5 Control(Path) 4 24.7 Temporal Ctx AD 3 Hippo 17.0 AD 1 Occipital Ctx 29.9 AD 4Hippo 18.6 AD 2 Occipital Ctx 0.0 (Missing) AD 5 Hippo 60.7 AD 3Occipital Ctx 8.3 AD 6 Hippo 12.2 AD 4 Occipital Ctx 20.4 Control 2Hippo 9.9 AD 5 Occipital Ctx 28.1 Control 4 Hippo 9.9 AD 6 Occipital Ctx22.4 Control (Path) 3 23.0 Control 1 Occipital 9.0 Hippo Ctx AD 1Temporal Ctx 45.1 Control 2 Occipital 55.9 Ctx AD 2 Temporal Ctx 76.3Control 3 Occipital 39.8 Ctx AD 3 Temporal Ctx 12.2 Control 4 Occipital12.1 Ctx AD 4 Temporal Ctx 47.3 Control (Path) 1 92.0 Occipital Ctx AD 5Inf Temporal 66.0 Control (Path) 2 28.1 Ctx Occipital Ctx AD 5 SupTemporal 39.2 Control (Path) 3 4.2 Ctx Occipital Ctx AD 6 Inf Temporal92.0 Control (Path) 4 35.4 Ctx Occipital Ctx AD 6 Sup Temporal 100.0Control 1 Parietal 8.6 Ctx Ctx Control 1 Temporal 7.7 Control 2 Parietal27.2 Ctx Ctx Control 2 Temporal 27.0 Control 3 Parietal 40.6 Ctx CtxControl 3 Temporal 27.0 Control (Path) 1 38.7 Ctx Parietal Ctx Control 3Temporal 6.5 Control (Path) 2 29.9 Ctx Parietal Ctx Control (Path) 156.3 Control (Path) 3 13.7 Temporal Ctx Parietal Ctx Control (Path) 250.7 Control (Path) 4 41.2 Temporal Ctx Parietal Ctx

[0646] TABLE CC General_screening_panel_v1.4 Rel. Exp. (%) Rel. Exp. (%)Ag4462, Ag4462, Tissue Name Run 222566753 Tissue Name Run 222566753Adipose 3.3 Renal ca. TK-10 2.0 Melanoma* 33.0 Bladder 6.0 Hs688(A).TMelanoma* 27.2 Gastric ca. (liver met.) NCI-N87 54.7 Hs688(B).TMelanoma* MM 1.6 Gastric ca. KATO III 19.9 Melanoma* 5.1 Colon ca.SW-948 0.9 LOXIMVI Melanoma* 1.0 Colon ca. SW480 3.6 SK-MEL-5 Squamouscell 3.1 Colon ca.* (SW480 met) 0.6 carcinoma SCC-4 SW620 Testis Pool8.4 Colon ca. HT29 0.3 Prostate ca.* (bone 14.4 Colon ca. HCT-116 0.2met) PC-3 Prostate Pool 8.0 Colon ca. CaCo-2 16.3 Placenta 1.7 Coloncancer tissue 3.9 Uterus Pool 5.2 Colon ca. SW1116 0.5 Ovarian ca.OVCAR-3 1.9 Colon ca. Colo-205 1.5 Ovarian ca. SK-OV-3 16.4 Colon ca.SW-48 0.8 Ovarian ca. OVCAR-4 5.6 Colon Pool 30.1 Ovarian ca. OVCAR-532.3 Small Intestine Pool 16.3 Ovarian ca. IGROV-1 2.9 Stomach Pool 7.5Ovarian ca. OVCAR- 6.4 Bone Marrow Pool 27.9 8 Ovary 10.7 Fetal Heart4.5 Breast ca. MCF-7 1.6 Heart Pool 8.1 Breast ca MDA-MB- 29.3 LymphNode Pool 35.6 231 Breast ca. BT 549 4.7 Fetal Skeletal Muscle 6.1Breast ca. T47D 26.2 Skeletal Muscle Pool 5.2 Breast ca. MDA-N 6.0Spleen Pool 2.2 Breast Pool 35.6 Thymus Pool 13.9 Trachea 14.6 CNScancer (glio/astro) 5.8 U87-MG Lung 7.7 CNS cancer (glio/astro) 100.0U-118-MG Fetal Lung 21.8 CNS cancer (neuro: met) 1.9 SK-N-AS Lung ca.NCI-N417 0.0 CNS cancer (astro) SF-589 23.8 Lung ca. LX-1 2.9 CMS cancer(astro) SNB-75 91.4 Lung ca. NCI-H146 0.2 CNS cancer (glio) SNB- 3.7 19Lung ca. SHP-77 0.0 CNS cancer (glio) SF- 33.7 295 Lung ca. A549 16.7Brain (Amygdala) Pool 0.8 Lung ca. NCI-H526 0.5 Brain (cerebellum) 1.5Lung ca. NCI-H23 14.4 Brain (fetal) 9.6 Lung ca. NCI-H460 27.2 Brain(Hippocampus) Pool 2.6 Lung ca. HOP-62 10.7 Cerebral Cortex Pool 2.1Lung ca. NCI-H522 0.0 Brain (Substantia nigra) Pool 1.7 Liver 0.5 Brain(Thalamus) Pool 2.8 Fetal Liver 1.0 Brain (whole) 2.0 Liver ca. HepG20.0 Spinal Cord Pool 2.0 Kidney Pool 25.9 Adrenal Gland 2.9 Fetal Kidney53.2 Pituitary gland Pool 1.2 Renal ca. 786-0 4.5 Salivary Gland 2.0Renal ca. A498 4.0 Thyroid (female) 1.8 Renal ca. ACHN 22.4 Pancreaticca. CAPAN2 23.0 Renal ca. UO-31 16.8 Pancreas Pool 34.2

[0647] TABLE CD Panel 4.1D Rel. Exp. (%) Rel. Exp. (%) Ag4462, Ag4462,Tissue Name Run 44579105 Tissue Name Run 44579105 Secondary Th1 act 16.0HUVEC IL-1beta 32.3 Secondary Th2 act 3.5 HUVEC IFN gamma 27.5 SecondaryTr1 act 10.9 HUVEC TNF alpha + IFN 26.6 gamma Secondary Th1 rest 1.6HUVEC TNF alpha + IL4 69.7 Secondary Th2 rest 0.3 HUVEC IL-11 25.2Secondary Tr1 rest 0.8 Lung Microvascular EC 100.0 none Primary Th1 act5.2 Lung Microvascular EC 97.3 TNFalpha + IL-1beta Primary Th2 act 1.1Microvascular Dermal EC 43.8 none Primary Tr1 act 6.1 MicrosvasularDermal EC 53.6 TNFalpha + IL-1beta Primary Th1 rest 2.5 Bronchialepithelium 7.9 TNFalpha + IL-1beta Primary Th2 rest 0.0 Small airwayepithelium 5.5 Primary Tr1 rest 0.0 Small airway epithelium 10.2TNFalpha + IL-1beta CD45RA CD4 3.2 Coronery artery SMC rest 19.6lymphocyte act CD45RO CD4 0.0 Coronery artery SMC 13.7 lymphocyte actTNFalpha + IL-1beta CD8 lymphocyte act 0.0 Astrocytes rest 28.1Secondary CD8 0.0 Astrocytes TNFalpha + IL- 17.6 lymphocyte rest 1betaSecondary CD8 0.5 KU-812 (Basophil) rest 0.0 lymphocyte act CD4lymphocyte none 2.4 KU-812 (Basophil) 0.7 PMA/ionomycin 2ryTh1/Th2/Tr1_anti- 0.0 CCD1106 (Keratinocytes) 31.4 CD95 CH11 none LAKcells rest 0.9 CCD1106 (Keratinocytes) 9.0 TNFalpha + IL-1 beta LAKcells IL-2 1.7 Liver cirrhosis 3.7 LAK cells IL-2 + IL-12 1.8 NCI-H292none 9.7 LAK cells IL-2 + IFN 3.1 NCI-H292 IL-4 5.4 gamma LAK cellsIL-2 + IL-18 2.6 NCI-H292 IL-9 13.8 LAK cells 0.9 NCI-H292 1L-13 9.9PMA/ionomycin NK Cells IL-2 rest 6.0 NCI-H292 IFN gamma 11.2 Two Way MLR3 day 7.0 HPAEC none 39.0 Two Way MLR 5 day 0.8 HPAEC TNFalpha + IL-170.7 beta Two Way MLR 7 day 2.4 Lung fibroblast none 25.2 PBMC rest 2.8Lung fibroblast TNFalpha + 2.0 IL-1beta PBMC PWM 0.0 Lung fibroblastIL-4 16.4 PBMC PHA-L 0.0 Lung fibroblast IL-9 44.4 Ramos (B cell) none0.0 Lung fibroblast IL-13 46.0 Ramos (B cell) 0.0 Lung fibroblast IFNgamma 6.5 ionomycin B lymphocytes PWM 0.8 Dermal fibroblast CCD1070 25.0rest B lymphocytes CD40L 0.0 Dermal fibroblast CCD1070 6.5 and IL-4TNFalpha EOL-1 dbcAMP 0.0 Dermal fibroblast CCD1070 4.0 IL-1beta EOL-1dbcAMP 0.0 Dermal fibroblast IFN 3.0 PMA/ionomycin gamma Dendritic cellsnone 0.0 Dermal fibroblast IL-4 13.5 Dendritic cells LPS 0.0 DermalFibroblasts rest 6.4 Dendritic cells anti- 0.8 Neutrophils TNFa + LPS0.0 CD40 Monocytes rest 0.0 Neutrophils rest 0.8 Monocytes LPS 0.7 Colon1.5 Macrophages rest 0.0 Lung 3.8 Macrophages LPS 0.0 Thymus 11.2 HUVECnone 29.1 Kidney 15.2 HUVEC starved 48.3

[0648] TABLE CE general oncology screening panel_v_2.4 Rel. Exp. (%)Rel. Exp. (%) Ag4462, Ag4462, Tissue Name Run 268672046 Tissue Name Run268672046 Colon cancer 1 11.1 Bladder cancer NAT 2 0.4 Colon cancer NAT1 2.9 Bladder cancer NAT 3 0.3 Colon cancer 2 3.3 Bladder cancer NAT 424.0 Colon cancer NAT 2 1.8 Prostate adenocarcinoma 1 39.2 Colon cancer3 25.9 Prostate adenocarcinoma 2 2.8 Colon cancer NAT 3 10.4 Prostateadenocarcinoma 3 16.5 Colon malignant cancer 4 4.6 Prostateadenocarcinoma 4 6.3 Colon normal adjacent tissue 4 1.9 Prostate cancerNAT 5 5.6 Lung cancer 1 18.7 Prostate adenocarcinoma 6 5.3 Lung NAT 11.6 Prostate adenocarcinoma 7 5.9 Lung cancer 2 56.6 Prostateadenocarcinoma 8 2.5 Lung NAT 2 1.8 Prostate adenocarcinoma 9 16.5Squamous cell carcinoma 3 12.0 Prostate cancer NAT 10 3.5 Lung NAT 3 0.5Kidney cancer 1 42.3 metastatic melanoma 1 13.4 Kidney NAT 1 9.1Melanoma 2 0.6 Kidney cancer 2 71.7 Mclanoma 3 0.3 Kidney NAT 2 13.5metastatic melanoma 4 46.7 Kidney cancer 3 37.1 metastatic melanoma 5100.0 Kidney NAT 3 3.1 Bladder cancer 1 4.1 Kidney cancer 4 7.1 Bladdercancer NAT 1 0.0 Kidney NAT 4 1.3 Bladder cancer 2 3.6

[0649] CNS_neurodegeneration_v1.0 Summary: Ag4462 This panel confirmsthe expression of this gene at low levels in the brain in an independentgroup of individuals. This gene is found to be upregulated in thetemporal cortex of Alzheimer's disease patients. Therefore, therapeuticmodulation of the expression or function of this gene may decreaseneuronal death and be of use in the treatment of this disease.

[0650] General_screening_panel_v1.4 Summary: Ag4462 Highest expressionof this gene is seen in a brain cancer cell line (CT=29.5). This gene iswidely expressed in this panel, with moderate to low expression seen inbrain, colon, gastric, lung, breast, ovarian, and melanoma cancer celllines. This expression profile suggests a role for this gene product incell survival and proliferation. Modulation of this gene product may beuseful in the treatment of cancer.

[0651] Among tissues with metabolic function, this gene is expressed atmoderate to low levels in adipose, adrenal gland, pancreas, and adultand fetal skeletal muscle and heart. This widespread expression amongthese tissues suggests that this gene product may play a role in normalneuroendocrine and metabolic function and that disregulated expressionof this gene may contribute to neuroendocrine disorders or metabolicdiseases, such as obesity and diabetes.

[0652] This gene is also expressed at low but significant levels in theCNS, including the hippocampus and thalamus. Therefore, therapeuticmodulation of the expression or function of this gene may be useful inthe treatment of neurological disorders.

[0653] Panel 4.1D Summary: Ag4462 This transcript is expressed at higherlevels in endothelial cells, with highest expression seen in untreatedlung microvascular EC (CT=31). Expression is also seen in samplesderived from HPAEC, HUVEC and lung microvascular EC, as well as lung anddermal fibroblasts. Therapies designed with the protein encoded by thistranscript could be important in regulating endothelium functionincluding leukocyte extravasation, a major component of inflammationduring asthma, IBD, and psoriasis.

[0654] general oncology screening panel_v_(—)2.4 Summary: Ag4462 Thisgene is widely expressed in this panel, with highest expression in asample derived from metastatic melanoma (CT=31.2). In addition, thisgene is more highly expressed in lung and kidney cancer than in thecorresponding normal adjacent tissue. Thus, expression of this genecould be used as a marker of these cancers. Furthemore, therapeuticmodulation of the expression or function of this gene product may beuseful in the treatment of lung and kidney cancer.

[0655] D. CG122759-01: Guanine Nucleotide Exchange Factor

[0656] Expression of gene CG122759-01 was assessed using theprimer-probe set Ag4535, described in Table DA. Results of the RTQ-PCRruns are shown in Tables DB and DC. TABLE DA Probe Name Ag4535 Start SEQID Primers Sequences Length Position No Forward5′-aacgggcacattaactttaagc-3′ 22 1057 98 ProbeTET-5′-ttctgggagatctccagacagatcca-3′-TAMRA 26 1084 99 Reverse5′-ctgtgtccatgtcatgaactca-3′ 22 1110 100

[0657] TABLE DB CNS neurodegeneration v1.0 Rel. Exp. Rel. Exp. (%) (%)Ag4535, Ag4535, Run Run Tissue Name 224702761 Tissue Name 224702761 AD 1Hippo 11.8 Control (Path) 3 7.5 Temporal Ctx AD 2 Hippo 14.1 Control(Path) 4 31.2 Temporal Ctx AD 3 Hippo 7.9 AD 1 Occipital Ctx 10.4 AD 4Hippo 5.0 AD 2 Occipital Ctx 0.0 (Missing) AD 5 hippo 97.3 AD 3Occipital Ctx 4.2 AD 6 Hippo 55.1 AD 4 Occipital Ctx 12.1 Control 2Hippo 37.1 AD 5 Occipital Ctx 20.4 Control 4 Hippo 7.9 AD 6 OccipitalCtx 49.3 Control (Path) 3 9.5 Control 1 Occipital 0.0 Hippo Ctx AD 1Temporal Ctx 10.2 Control 2 Occipital 50.3 Ctx AD 2 Temporal Ctx 19.2Control 3 Occipital 10.4 Ctx AD 3 Temporal Ctx 3.4 Control 4 Occipital0.0 Ctx AD 4 Temporal Ctx 18.0 Control (Path) 1 100.0 Occipital Ctx AD 5Inf Temporal 92.0 Control (Path) 2 6.4 Ctx Occipital Ctx AD 5 SupTemporal 27.9 Control (Path) 3 2.6 Ctx Occipital Ctx AD 6 Inf Temporal35.4 Control (Path) 4 5.9 Ctx Occipital Ctx AD 6 Sup Temporal 47.3Control 1 Parietal 6.1 Ctx Ctx Control 1 Temporal 2.4 Control 2 Parietal38.4 Ctx Ctx Control 2 Temporal 39.0 Control 3 Parietal 11.0 Ctx CtxControl 3 Temporal 12.5 Control (Path) 1 76.8 Ctx Parietal Ctx Control 4Temporal 6.9 Control (Path) 2 8.8 Ctx Parietal Ctx Control (Path) 1 42.6Control (Path) 3 0.0 Temporal Ctx Parietal Ctx Control (Path) 2 39.2Control (Path) 4 50.3 Temporal Ctx Parietal Ctx

[0658] TABLE DC General_screening_panel_v1.4 Rel. Exp. (%) Rel. Exp. (%)Ag4535, Ag4535, Tissue Name Run 222735447 Tissue Name Run 222735447Adipose 0.0 Renal ca. TK-10 6.9 Melanoma* 0.0 Bladder 6.0 Hs688(A).TMelanoma* 0.0 Gastric ca. (liver met.) 0.0 Hs688(B).T NCI-N87 Melanoma*M14 0.0 Gastric ca. KATO III 0.0 Melanoma* 0.0 Colon ca. SW-948 0.0LOXIMVI Melanoma* SK- 25.2 Colon ca. SW480 0.0 MEL-5 Squamous cell 0.0Colon ca.* (SW480 met) 0.0 carcinoma SCC-4 SW620 Testis Pool 0.0 Colonca. HT29 0.0 Prostate ca.* (bone 0.0 Colon ca. HCT-116 46.7 met) PC-3Prostate Pool 0.0 Colon ca. CaCo-2 5.0 Placenta 5.2 Colon cancer tissue0.0 Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. OVCAR-3 10.0 Colonca. Colo-205 0.0 Ovarian ca. SK-OV-3 0.0 Colon ca. SW-48 0.0 Ovarian ca.OVCAR-4 13.5 Colon Pool 0.0 Ovarian ca. OVCAR-5 13.6 Small IntestinePool 0.0 Ovarian ca. IGROV-1 33.2 Stomach Pool 0.0 Ovarian ca. OVCAR-0.0 Bone Marrow Pool 0.0 8 Ovary 0.0 Fetal Heart 0.0 Breast ca. MCF-70.0 Heart Pool 0.0 Breast ca. MDA-MB-231 0.0 Lymph Node Pool 2.6 Breastca. BT 549 0.0 Fetal Skeletal Muscle 0.0 Breast ca. T47D 0.0 SkeletalMuscle Pool 0.0 Breast ca. MDA-N 0.0 Spleen Pool 4.8 Breast Pool 0.0Thymus Pool 0.0 Trachea 2.4 CNS cancer (glio/astro) 0.0 U87-MG Lung 0.0CNS cancer (glio/astro) 0.0 U-118-MG Fetal Lung 0.0 CNS cancer (neuro:met) 0.0 SK-N-AS Lung ca. NCI-N417 0.0 CNS cancer (astro) SF- 0.0 539Lung ca. LX-1 9.3 CNS cancer (astro) 5.0 SNB-75 Lung ca. NCI-H146 6.7CNS cancer (glio) SNB- 18.9 19 Lung ca. SHP-77 11.9 CNS cancer (glio)SF- 0.0 295 Lung ca. A549 3.3 Brain (Amygdala) Pool 22.2 Lung ca.NCI-H526 0.0 Brain (cerebellum) 71.7 Lung ca. NCI-H23 55.1 Brain (fetal)27.2 Lung ca. NCI-H460 3.6 Brain (Hippocampus) Pool 18.4 Lung ca. HOP-620.0 Cerebial Cortex Pool 34.6 Lung ca. NCI-H522 5.0 Brain (Substantianigra) 19.1 Pool Liver 0.0 Brain (Thalamus) Pool 34.9 Fetal Liver 0.0Brain (whole) 54.7 Liver ca. HepG2 8.1 Spinal Cord Pool 11.8 Kidney Pool2.4 Adrenal Gland 2.2 Fetal Kidney 0.0 Pituitary gland Pool 3.2 Renalca. 786-0 0.0 Salivary Gland 2.7 Renal ca. A498 100.0 Thyroid (female)0.0 Renal ca. ACHN 0.0 Pancreatic ca. CAPAN2 10.7 Renal ca. UO-31 0.0Pancreas Pool 5.0

[0659] CNS_neurodegeneration_v1.0 Summary: Ag4535 This panel does notshow differential expression of this gene in Alzheimer's disease.However, this expression profile confirms the presence of this gene inthe brain. Therefore, therapeutic modulation of the expression orfunction of this gene may be useful in the treatment of neurologicaldisorders, such as Alzheimer's disease, Parkinson's disease,schizophrenia, multiple sclerosis, stroke and epilepsy.

[0660] General_screening_panel_v1.4 Summary: Ag4535 Expression of thisgene is restricted to a sample derived from a kidney cancer cell lineand the cerebellum(CTs=34-35). Thus, therapeutic modulation of theexpression or function of this gene may be effective in the treatment ofkidney cancer.

[0661] Panel 4.1D Summary: Ag4535 Expression of this gene islow/undetectable in all samples on this panel (CTs>35).

[0662] E. CG122759-02: Guanine Nucleotide Exchange Factor

[0663] Expression of gene full length physical clone CG122759-02, avariant of CG1227598-01 above, was assessed using the primer-probe setAg6816, described in Table EA. Results of the RTQ-PCR runs are shown inTables EB and EC. TABLE EA Probe Name Ag6816 Primers Sequences LengthStart Position SEQ ID No Forward 5′-tgccgggtggtgaaga-3′ 16 688 101 ProbeTET-5′-actccaacatgcgggcccggt-3′-TAMRA 21 710 102 Reverse5′-actcccgggccacatc-3′ 16 739 103

[0664] TABLE EB CNS_neurodegeneration_v1.0 Rel. Rel. Exp. (%) Exp. (%)Ag6816, Ag6816, Run Run Tissue Name 278022737 Tissue Name 278022737 AD 1Hippo 11.8 Control (Path) 3 2.8 Temporal Ctx AD 2 Hippo 19.5 Control(Path) 4 35.6 Temporal Ctx AD 3 Hippo 17.8 AD 1 Occipital Ctx 6.1 AD 4Hippo 3.5 AD 2 Occipital Ctx 0.0 (Missing) AD 5 hippo 100.0 AD 3Occipital Ctx 3.0 AD 6 Hippo 50.0 AD 4 Occipital Ctx 12.2 Control 2Hippo 55.1 AD 5 Occipital Ctx 13.4 Control 4 Hippo 8.8 AD 6 OccipitalCtx 38.2 Control (Path) 3 3.6 Control 1 Occipital 0.5 Hippo Ctx AD 1Temporal Ctx 14.1 Control 2 Occipital 87.7 Ctx AD 2 Temporal Ctx 17.1Control 3 Occipital 15.2 Ctx AD 3 Temporal Ctx 6.0 Control 4 Occipital1.7 Ctx AD 4 Temporal Ctx 12.6 Control (Path) 1 84.7 Occipital Ctx AD 5Inf Temporal 62.0 Control (Path) 2 1.7 Ctx Occipital Ctx AD 5SupTemporal 45.1 Control (Path) 3 0.8 Ctx Occipital Ctx AD 6 InfTemporal 43.2 Control (Path) 4 4.9 Ctx Occipital Ctx AD 6 Sup Temporal26.2 Control 1 Parietal 2.5 Ctx Ctx Control 1 Temporal 0.6 Control 2Parietal 26.4 Ctx Ctx Control 2 Temporal 47.6 Control 3 Parietal 10.7Ctx Ctx Control 3 Temporal 13.7 Control (Path) 1 70.7 Ctx Parietal CtxControl 4 Temporal 2.6 Control (Path) 2 18.6 Ctx Parietal Ctx Control(Path) 1 62.4 Control (Path) 3 1.7 Temporal Ctx Parietal Ctx Control(Path) 2 45.1 Control (Path) 4 18.2 Temporal Ctx Parietal Ctx

[0665] TABLE EC Panel 4.1D Rel. Rel. Exp. (%) Exp. (%) Ag6816, Ag6816,Run Run Tissue Name 278022639 Tissue Name 278022639 Secondary Th1 act5.4 HUVEC IL-1beta 1.8 Secondary Th2 act 4.2 HUVEC IFN gamma 0.0Sccondary Tr1 act 1.8 HUVEC TNF alpha + IFN 0.0 gamma Secondary Th1 rest14.1 HUVEC TNF alpha + IL4 0.0 Secondary Th2 rest 0.0 HUVEC IL-11 0.0Secondary Tr1 rest 10.0 Lung Microvascular EC 0.0 none Primary Th1 act0.0 Lung Microvascular EC 0.0 TNFalpha + IL-1beta Primary Th2 act 0.0Microvascular Dermal EC 0.0 none Primary Tr1 act 0.0 MicrosvasularDermal EC 0.0 TNFalpha + IL-1beta Primary Th1 rest 2.0 Bronchialepithelium 23.0 TNFalpha + IL1beta Primary Th2 rest 0.0 Small airwayepithelium 70.7 none Primary Tr1 rest 0.0 Small airway epithelium 100.0TNFalpha + IL-1beta CD45RA CD4 0.0 Coronery artery SMC rest 0.0lymphocyte act CD45RO CD4 5.0 Coronery artery SMC 0.0 lymphocyte actTNFalpha + IL-1beta CD8 lymphocyte act 4.1 Astrocytes rest 0.0 SecondaryCD8 0.0 Astrocytes TNFalpha + IL- 0.0 lymphocyte rest 1beta SecondaryCD8 0.0 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte none0.0 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti- 7.5CCD1106 (Keratinocytes) 70.2 CD95 CH11 none LAK cells rest 0.0 CCD1106(Keratinocytes) 28.9 TNFalpha + IL-1beta LAK cells IL-2 12.9 Livercirrhosis 0.0 LAK cells IL-2 + IL-12 0.0 NCI-H292 none 0.0 LAK cellsIL-2 + IFN 0.0 NCI-H292 IL-4 0.0 gamma LAK cells IL-2 + IL-18 0.0NCI-H292 IL-9 0.0 LAK cells 0.0 NCI-H292 IL-13 0.0 PMA/ionomycin NKCells IL-2 rest 40.1 NCI-H292 IFN gamma 0.0 Two Way MLR 3 day 0.0 HPAECnone 0.0 Two Way MLR 5 day 0.0 HPAEC TNF alpha + IL-1 0.0 beta Two WayMLR 7 day 0.0 Lung fibroblast none 0.0 PBMC rest 0.0 Lung fibroblast TNFalpha + 0.0 IL-1 beta PBMC PWM 0.0 Lung fibroblast IL-4 0.0 PBMC PHA-L0.0 Lung fibroblast IL-9 0.0 Ramos (B cell) none 0.0 Lung fibroblastIL-13 0.0 Ramos (B cell) 0.0 Lung fibroblast IFN gamma 3.3 ionomycin Blymphocytes PWM 0.0 Dermal fibroblast CCD1070 rest 0.0 B lymphocytesCD40L 0.0 Dermal fibroblast CCD1070 TNF alpha 81.2 and IL-4 EOL-1 dbcAMP0.0 Dermal fibroblast CCD1070 IL-1 beta 0.0 EOL-1 dbcAMP 0.0 Dermalfibroblast IFN 0.0 PMA/ionomycin gamma Dendritic cells none 0.0 Dermalfibroblast IL-4 6.5 Dendritic cells LPS 0.0 Dermal Fibroblasts rest 0.0Dendritic cells anti- 0.0 Neutrophils TNFa + LPS 0.0 CD40 Monocytes rest0.0 Neutrophils rest 18.6 Monocytes LPS 0.0 Colon 0.0 Macrophages rest0.0 Lung 0.0 Macrophages LPS 1.8 Thymus 0.0 HUVEC none 0.0 Kidney 21.8HUVEC starved 0.0

[0666] CNS_neurodegeneration_v1.0 Summary: Ag6816 This panel does notshow differential expression of this gene in Alzheimer's disease.However, this expression profile confirms the presence of this gene inthe brain. Therefore, therapeutic modulation of the expression orfunction of this gene may be useful in the treatment of neurologicaldisorders, such as Alzheimer's disease, Parkinson's disease,schizophrenia, multiple sclerosis, stroke and epilepsy.

[0667] Panel 4.1D Summary: Ag6816 Expression of this gene is limited toactivated and untreated small airway epithelium, untreatedkertainocytes, and TNF alpha treated dermal fibroblasts (CTs=34-35).Thus, expression of this gene could be used to differentiate thesesamples from the other samples on this panel.

[0668] F. CG124599-01: MAXP1

[0669] Expression of gene CG124599-01 was assessed using theprimer-probe sets Ag4671 and Ag4674, described in Tables FA and FB.Results of the RTQ-PCR runs are shown in Tables FC, FD, FE and FF. TABLEFA Probe Name Ag4671 Start SEQ ID Primers Sequences Length Position NoForward 5′-aggtagagtgggatgccttct-3′ 21 1096 104 ProbeTET-5′-ccatccctgaacttcagaacttcctaaca-3′-TAMRA 29 1117 105 Reverse5′-gattttgtcctgctcctctttt-3′ 22 1154 106

[0670] TABLE FB Probe Name Ag4674 Primers Sequences Length StartPosition SEQ ID No Forward 5′-gctcttccagaaactctccatt-3′ 22 989 107 ProbeTET-5′-ctctacctgcgcctgcttgctgg-3′-TAMRA 23 1023 108 Reverse5′-tcattctcctttagcacaaagc-3′ 22 1066 109

[0671] TABLE FC CNS_neurodegeneration_v1.0 Rel. Rel. Exp. (%) Exp. (%)Ag4671, Ag4671, Run Run Tissue Name 224702763 Tissue Name 224702763 AD 1Hippo 14.1 Control (Path) 3 4.5 Temporal Ctx AD 2 Hippo 26.8 Control(Path) 4 32.3 Temporal Ctx AD 3 Hippo 7.7 AD 1 Occipital Ctx 22.7 AD 4Hippo 4.2 AD 2 Occipital Ctx 0.0 (Missing) AD 5 hippo 100.0 AD 3Occipital Ctx 6.2 AD 6 Hippo 57.8 AD 4 Occipital Ctx 13.4 Control 2Hippo 26.4 AD 5 Occipital Ctx 35.6 Control 4 Hippo 8.9 AD 6 OccipitalCtx 36.9 Control (Path) 3 4.3 Control 1 Occipital 7.5 Hippo Ctx AD 1Temporal Ctx 15.3 Control 2 Occipital 51.1 Ctx AD 2 Temporal Ctx 19.3Control 3 Occipital 19.5 Ctx AD 3 Temporal Ctx 8.8 Control 4 Occipital4.8 Ctx AD 4 Temporal Ctx 9.7 Control (Path) 1 77.9 Occipital Ctx AD 5Inf Temporal 73.7 Control (Path) 2 15.0 Ctx Occipital Ctx AD 5SupTemporal 36.6 Control (Path) 3 1.5 Ctx Occipital Ctx AD 6 InfTemporal 53.6 Control (Path) 4 21.0 Ctx Occipital Ctx AD 6 Sup Temporal45.7 Control 1 Parietal 6.5 Ctx Ctx Control 1 Temporal 7.2 Control 2Parietal 30.8 Ctx Ctx Control 2 Temporal 32.1 Control 3 Parietal 31.9Ctx Ctx Control 3 Temporal 13.0 Control (Path) 1 75.8 Ctx Parietal CtxControl 4 Temporal 5.6 Control (Path) 2 31.2 Ctx Parietal Ctx Control(Path) 1 65.5 Control (Path) 3 2.2 Temporal Ctx Parietal Ctx Control(Path) 2 40.3 Control (Path) 4 52.9 Temporal Ctx Parietal Ctx

[0672] TABLE FD General_screening_panel_v1.4 Rel. Exp. (%) Rel. Exp. (%)Rel. Exp. (%) Rel. Exp. (%) Ag4671, Run Ag4674, Run Ag4671, Run Ag4674,Run Tissue Name 222811513 222811526 Tissue Name 222811513 222811526Adipose 17.1 6.6 Renal ca. TK-10 7.9 5.0 Melanoma* 5.0 5.3 Bladder 43.526.1 Hs688(A).T Melanoma* 6.9 7.0 Gastric ca. (liver 100.0 100.0Hs688(B).T met.) NCI-N87 Melanoma* 1.5 0.8 Gastric ca. KATO 22.4 26.1M14 III Melanoma* 1.4 1.1 Colon ca. SW-948 7.1 5.4 LOXIMVI Melanoma* 4.72.9 Colon ca. SW480 23.3 21.9 SK-MEL-5 Squamous cell 9.4 8.2 Colon ca.*6.3 4.7 carcinoma (SW480 met) SCC-4 SW620 Testis Pool 5.6 1.9 Colon ca.HT29 9.7 8.0 Prostate ca.* 21.9 18.7 Colon ca. HCT- 12.3 8.9 (bone met)116 PC-3 Prostate Pool 7.2 3.8 Colon ca. CaCo-2 2.3 1.0 Placenta 3.0 4.6Colon cancer 16.4 11.5 tissue Uterus Pool 4.9 2.2 Colon ca. 2.4 1.7SW1116 Ovarian ca. 0.8 0.6 Colon ca. Colo-205 15.9 13.2 OVCAR-3 Ovarianca. 3.0 2.4 Colon ca. SW-48 0.4 0.3 SK-OV-3 Ovarian ca 3.2 2.1 ColonPool 11.1 6.3 OVCAR-4 Ovarian ca. 26.4 18.4 Small Intestine 5.6 3.7OVCAR-5 Pool Ovarian ca 1.8 0.5 Stomach Pool 5.8 4.7 IGROV-1 Ovarian ca.1.0 1.7 Bone Marrow 9.5 0.9 OVCAR-8 Pool Ovary 8.1 6.2 Fetal Heart 2.61.8 Breast ca. 2.5 2.1 Heart Pool 3.2 2.3 MCF-7 Breast ca. 8.8 7.7 LymphNode Pool 11.7 8.2 MDA-MB-231 Breast ca. BT 0.5 0.3 Fetal Skeletal 2.32.3 549 Muscle Breast ca. 49.0 33.7 Skeletal Muscle 8.6 5.4 T47D PoolBreast ca 0.5 0.4 Spleen Pool 62.9 45.7 MDA-N Breast Pool 9.8 6.9 ThymusPool 44.8 28.9 Trachea 40.1 32.5 CNS cancer 4.2 3.6 (glio/astro) U87- MGLung 1.6 0.3 CNS cancer 3.1 2.8 (glio/astro) U- 118-MG Fetal Lung 32.821.2 CNS cancer 1.6 1.2 (neuro:met) SK-N-AS Lung ca. NCI-N417 0.1 0.0CNS cancer 13.3 12.0 (astro) SF-539 Lung ca. LX-1 6.3 7.0 CNS cancer 2.91.2 (astro) SNB-75 Lung ca. NCI- 4.9 3.2 CNS cancer (glio) 0.9 0.7 H146SNB-19 Lung ca. SHP-77 37.9 32.1 CNS cancer (glio) 13.8 11.3 SF-295 Lungca. A549 9.7 9.7 Brain (Amygdala) 9.7 8.8 Pool Lung ca. NCI- 5.8 4.7Brain 11.0 7.2 H526 (cerebellum) Lung ca. NCI- 3.9 2.9 Brain (fetal) 5.23.3 H23 Lung ca. NCI- 1.1 0.8 Brain 10.7 10.3 H460 (Hippocampus) PoolLung ca. HOP- 7.6 11.7 Cerebral Cortex 19.8 11.0 62 Pool Lung ca. NCI-1.7 1.4 Brain (Substantia 9.8 11.4 H522 nigra) Pool Liver 5.4 3.7 Brain(Thalamus) 22.8 29.3 Pool Fetal Liver 14.6 12.3 Brain (whole) 23.7 15.5Liver ca. 0.9 0.8 Spinal Cord Pool 6.3 4.5 HepG2 Kidney Pool 14.0 11.7Adrenal Gland 26.6 24.8 Fetal Kidney 3.1 3.1 Pituitary gland 5.9 4.2Pool Renal ca. 786- 9.5 8.7 Salivary Gland 31.9 33.2 0 Renal ca. 2.9 1.5Thyroid (female) 7.5 5.3 A498 Renal ca. 0.5 0.5 Pancreatic ca. 62.4 55.1ACHN CAPAN2 Renal ca. UO- 0.3 0.2 Pancreas Pool 15.4 9.4 31

[0673] TABLE FE Oncology_cell_line_screening_panel_v3.1 Rel. Rel. Exp.(%) Exp. (%) Ag4674, Ag4674, Run Run Tissue Name 224053017 Tissue Name224053017 Daoy 1.0 Ca Ski_Cervical epidermoid 6.8Medulloblastoma/Cerebellum carcinoma (metastasis) TE671 7.9 ES-2_Ovarianclear cell 0.1 Medulloblastom/Cerebellum carcinoma D283 Med 0.5 Ramos/6hstim_Stimulated with 6.3 Medulloblastoma/Cerebellum PMA/ionomycin 6hPFSK-1 Primitive 1.6 Ramos/14h stim_Stimulated with 7.3Neuroectodermal/Cerebellum PMA/ionomycin 14h XF-498_CNS 0.3MEG-01_Chronic myelogenous 12.8 leukemia (megokaryoblast)SNB-78_CNS/glioma 0.8 Raji_Burkitt's lymphoma 5.0SF-268_CNS/glioblastoma 0.3 Daudi_Burkitt's lymphoma 11.0T98G_Glioblastoma 2.3 U266_B-cell 42.6 plasmacytoma/myelomaSK-N-SH_Neuroblastoma 1.5 CA46_Burkitt's lymphoma 5.7 (metastasis)SF-295_CNS/glioblastoma 2.5 RL_non-Hodgkin's B-cell 6.2 lymphomaCerebellum 3.0 JM1_pre-B-cell 8.2 lymphoma/leukemia Cerebellum 1.6Jurkat_T cell leukemia 30.4 NCI-H292_Mucoepidermoid 17.3TF-1_Erythroleukemia 25.0 lung ca. DMS-114_Small cell lung 0.4 HUT78_T-cell lymphoma 100.0 cancer DMS-79_Small cell lung 3.3U937_Histiocytic lymphoma 17.9 cancer/neuroendocrine NCI-H146_Small celllung 2.9 KU-812_Myelogenous leukemia 10.7 cancer/neuroendocrineNCI-H526_Small cell lung 5.5 769-P_Clear cell renal ca. 0.3cancer/neuroendocrine NCI-N417_Small cell lung 0.0 Caki-2_Clear cellrenal ca 0.1 cancer/neuroendocrine NCI-H82_Small cell lung 0.7 SW839_Clear cell renal ca. 0.5 cancer/neuroendocrine NCI-H157_Squamouscell lung 0.2 G401_Wilms' tumor 0.2 cancer (metastasis) NCI-H1155_Largecell lung 3.7 Hs766T_Pancreatic ca. (LN 1.7 cancer/neuroendocrinemetastasis) NCI-H1299_Large cell lung 1.1 CAPAN-1_Pancreatic 2.8cancer/neuroendocrine adenocarcinoma (liver metastasis) NCI-H727_Lungcarcinoid 5.1 SU86.86_Pancreatic carcinoma 5.0 (liver metastasis)NCI-UMC-11_Lung carcinoid 17.4 BxPC-3_Pancreatic 2.8 adenocarcinomaLX-1_Small cell lung cancer 2.4 HPAC Pancreatic 7.5 adenocarcinomaColo-205_Colon cancer 8.7 MIA PaCa-2_Pancreatic ca. 0.0 KM12_Coloncancer 0.1 CFPAC-1_Pancreatic ductal 12.8 adenocarcinoma KM20L2_Coloncancer 0.5 PANC-1_Pancreatic epithelioid 0.2 ductal ca. NCI-H716_Coloncancer 1.5 T24_Bladder ca. (transitional cell) 0.0 SW-48_Colonadenocarcinoma 0.0 5637_Bladder ca. 0.8 SW1116_Colon 0.8 HT-1197_Bladderca. 0.5 adenocarcinoma LS 174T_Colon 0.0 UM-UC-3_Bladder ca. 0.0adenocarcinoma (transitional cell) SW-948_Colon adenocarcinoma 1.9A204_Rhabdomyosarcoma 0.1 SW-480_Colon adenocarcinoma 0.7HT-1080_Fibrosarcoma 2.7 NCI-SNU-5_Gastric ca. 3.3 MG-63_Osteosarcoma(bone) 0.8 KATO III_Stomach 2.8 SK-LMS-1_Leiomyosarcoma 2.3 (vulva)NCI-SNU-16_Gastric ca. 1.6 SJRH30_Rhabdomyosarcoma 1.4 (met to bonemarrow) NCI-SNU-1_Gastric ca. 0.0 A431_Epidermoid ca. 6.1 RF-1_Gastricadenocarcinoma 14.7 WM266-4_Melanoma 0.3 RF-48_Gastric adenocarcinoma17.7 DU 145_Prostate 2.6 MKN-45_Gastric ca. 0.8 MDA-MB-468_Breast 2.6adenocarcinoma NCI-N87_Gastric ca. 8.5 SSC-4_Tongue 2.0 OVCAR-5_Ovarianca. 0.8 SSC-9_Tongue 1.6 RL95-2_Uterine carcinoma 0.1 SSC-15_Tongue 4.9HelaS3_Cervical 4.1 CAL 27_Squamous cell ca. of 4.0 adenocarcinomatongue

[0674] TABLE FF Panel 4.1D Rel. Rel. Exp. (%) Exp. (%) Ag4671, Ag4671,Run Run Tissue Name 200755347 Tissue Name 200755347 Secondary Th1 act85.9 HUVEC IL-1beta 0.2 Secondary Th2 act 97.9 HUVEC IFN gamma 0.7Secondary Tr1 act 98.6 HUVEC TNF alpha + IFN gamma 1.0 Secondary Th1rest 23.8 HUVEC TNF alpha + IL4 0.1 Secondary Th2 rest 27.5 HUVEC IL-110.1 Secondary Tr1 rest 65.1 Lung Microvascular EC 0.4 none Primary Th1act 50.7 Lung Microvascular EC 2.4 TNFalpha + IL-1beta Primary Th2 act81.2 Microvascular Dermal EC 0.3 none Primary Tr1 act 79.6 MicrosvasularDermal EC 6.4 TNFalpha + IL-1beta Primary Th1 rest 24.5 Bronchialepithelium 2.2 TNFalpha + IL1beta Primary Th2 rest 15.6 Small airwayepithelium 0.7 none Primary Tr1 rest 33.9 Small airway epithelium 0.9TNFalpha + IL-1beta CD45RA CD4 33.0 Coronery artery SMC rest 0.7lymphocyte act CD45RO CD4 100.0 Coronery artery SMC 0.6 lymphocyte actTNFalpha + IL-1beta CD8 lymphocyte act 57.4 Astrocytes rest 0.2Secondary CD8 70.7 Astrocytes TNFalpha + IL- 4.6 lymphocyte rest 1betaSecondary CD8 43.5 KU-812 (Basophil) rest 6.4 lymphocyte act CD4lymphocyte none 26.4 KU-812 (Basophil) 16.5 PMA/ionomycin 2ryTh1/Th2/Tr1_anti- 44.8 CCD1106 (Keratinocytes) 0.3 CD95 CH11 none LAKcells rest 49.0 CCD1106 (Keratinocytes) 0.5 TNFalpha + IL-1beta LAKcells IL-2 47.3 Liver cirrhosis 2.9 LAK cells IL-2 + IL-12 23.8 NCI-H292none 7.8 LAK cells IL-2 + IFN 24.5 NCI-H292 IL-4 8.4 gamma LAK cellsIL-2 + IL-18 30.4 NCI-H292 IL-9 10.2 LAK cells 86.5 NCI-H292 IL-13 10.9PMA/ionomycin NK Cells IL-2 rest 73.7 NCI-H292 IFN gamma 6.2 Two Way MLR3 day 36.9 HPAEC none 0.3 Two Way MLR 5 day 36.6 HPAEC TNF alpha + IL-10.7 beta Two Way MLR 7 day 37.9 Lung fibroblast none 0.8 PBMC rest 27.7Lung flbroblast TNF alpha + IL-I beta 1.0 PBMC PWM 43.8 Lung fibroblastIL-4 0.4 PBMC PHA-L 49.0 Lung fibroblast IL-9 1.1 Ramos (B cell) none3.3 Lung fibroblast IL-13 1.2 Ramos (B cell) 5.8 Lung fibroblast IFNgamma 2.0 ionomycin B lymphocytes PWM 29.1 Dermal fibroblast CCD1070 2.6rest B lymphocytcs CD40L 26.8 Dermal fibrohlast CCD1070 42.6 and IL-4TNF alpha EOL-1 dbcAMP 21.0 Dermal fibroblast CCD1070 0.4 IL-1 betaEOL-1 dbcAMP 78.5 Dermal fibroblast IFN 3.5 PMA/ionomycin gammaDendritic cells none 10.7 Dermal fibroblast IL-4 4.9 Dendritic cells LPS7.5 Dermal Fibroblasts rest 6.8 Dendritic cells anti- 15.7 NeutrophilsTNFa + LPS 73.7 CD40 Monocytes rest 33.0 Neutrophils rest 54.7 MonocytesLPS 47.3 Colon 3.2 Macrophages rest 21.0 Lung 3.3 Macrophages LPS 18.8Thymus 35.6 HUVEC none 0.0 Kidney 2.8 HUVEC starved 0.2

[0675] CNS_neurodegeneration_v1.0 Summary: Ag4671 This panel confirmsthe expression of this gene at moderate levels in the brain in anindependent group of individuals. This gene appears to be slightlyupregulated in the temporal cortex of Alzheimer's disease patients.Therefore, therapeutic modulation of the expression or function of thisgene may decrease neuronal death and be of use in the treatment of thisdisease.

[0676] General_screening_panel_v1.4 Summary: Ag4671/Ag4674 Twoexperiments with two different probe and primer sets produce resultsthat are in excellent agreement, with highest expression of this gene isseen in a gastric cancer cell line (CTs=28). This gene is widelyexpressed in this panel, with moderate expression seen in brain, colon,gastric, lung, breast, ovarian, and melanoma cancer cell lines. Thisexpression profile suggests a role for this gene product in cellsurvival and proliferation. Modulation of this gene product may beuseful in the treatment of cancer.

[0677] Among tissues with metabolic function, this gene is expressed atmoderate to low levels in pituitary, adipose, adrenal gland, pancreas,thyroid, and adult and fetal skeletal muscle, heart, and liver. Thiswidespread expression among these tissues suggests that this geneproduct may play a role in normal neuroendocrine and metabolic functionand that disregulated expression of this gene may contribute toneuroendocrine disorders or metabolic diseases, such as obesity anddiabetes.

[0678] This gene is also expressed at moderate to low levels in the CNS,including the hippocampus, thalamus, substantia nigra, amygdala,cerebellum and cerebral cortex. Therefore, therapeutic modulation of theexpression or function of this gene may be useful in the treatment ofneurologic disorders, such as Alzheimer's disease, Parkinson's disease,schizophrenia, multiple sclerosis, stroke and epilepsy.

[0679] In addition, this gene is expressed at much higher levels infetal lungtissue (CTs=30) when compared to expression in the adultcounterpart (CTs=34-36). Thus, expression of this gene may be used todifferentiate between the fetal and adult source of this tissue.

[0680] Oncology_cell_line_screening_panel_v3.1 Summary: Ag4674 Highestexpression of this (gene is seen in a T cell lymphoma cell line(CT=27.3). In addition, moderate to low levels of expression are seen inmost of the cell lines on this panel. This expression is in agreementwith expression seen in Panel 1.4. Please see Panel 1.4 for discussionof this gene in cancer.

[0681] Panel 4.1D Summary: Ag4671 Highest expression of this gene isseen in activated CD45RO CD4 lymphocytes (CT=27). In addition, thistranscript is expressed at high levels in in T cells, particularlychronically activated Th1, Th2 and Tr1 cells. Macrophages, B cells, LAKcells, eosinophils, monocytes and dendritic cells also express thetranscript. Thus, this transcript or the protein it encodes could beused to detect hematopoietically-derived cells. Furthermore,therapeutics designed with the protein encoded by this transcript couldbe important in the regulation of the function of antigen presentingcells (macrophages and dendritic cells) or T cells and be important inthe treatment of asthma, emphysema, psoriasis, arthritis, and IBD.

[0682] G. CG125414-01 and CG125414-02: XAF-1 with Zinc Finger Motif

[0683] Expression of gene CG125414-01 and full length physical cloneCG125414-02 was assessed using the primer-probe set Ag6580, described inTable GA Results of the RTQ-PCR runs are shown in Tables GB and GC.Please note that CG125414-02 represents a full-length physical clone ofthe CG125414-01 gene, validating the prediction of the gene sequence.TABLE GA Probe Name Ag6580 Start SEQ ID Primers Sequences LengthPosition No Forward 5′-tccacgatggagaaagatgt-3′ 20 553 110 ProbeTET-5′-tcctcttcattctgaaagttcatcaaa-3′-TAMRA 27 603 111 Reverse5′-ttttgcttcttggtgctttc-3′ 20 630 112

[0684] TABLE GB General_screening_panel_v1.6 Rel. Rel. Exp. (%) Exp. (%)Ag6580, Ag6580, Run Run Tissue Name 277255894 Tissue Name 277255894Adipose 4.3 Renal ca. TK-10 0.0 Melanoma* 4.3 Bladder 55.9 Hs688 (A).TMelanoma* 7.4 Gastric ca. (liver met.) NCI-N87 100.0 Hs688 (B).TMelanoma* M14 3.9 Gastric ca. KATO III 5.6 Melanoma* 0.0 Colon ca.SW-948 0.0 LOXIMVI Melanoma* SK- 0.1 Colon ca. SW480 0.0 MEL-5 Squamouscell 0.9 Colon ca.* (SW480 met) 0.0 carcinoma SCC-4 SW620 Testis Pool3.8 Colon ca. HT29 0.0 Prostate ca.* (bone met) PC-3 0.0 Colon ca.HCT-116 0.0 Prostate Pool 5.6 Colon ca. CaCo-2 0.0 Placenta 0.4 Coloncancer tissue 2.3 Uterus Pool 1.2 Colon ca. SW1116 0.0 Ovarian ca.OVCAR- 0.0 Colon ca. Colo-205 0.9 3 Ovarian ca. SK-OV-3 0.7 Colon ca.SW-48 0.0 Ovarian ca. OVCAR- 0.1 Colon Pool 5.0 4 Ovarian ca. OVCAR- 4.6Small Intestine Pool 3.6 5 Ovarian ca. IGROV-1 0.0 Stomach Pool 2.0Ovarian ca. OVCAR- 0.2 Bone Marrow Pool 3.3 8 Ovary 12.5 Fetal Heart 1.8Breast ca. MCF-7 0.0 Heart Pool 2.3 Breast ca. MDA-MB-231 3.6 Lymph NodePool 0.0 Breast ca. BT 549 16.5 Fetal Skeletal Muscle 3.5 Breast ca.T47D 0.0 Skeletal Muscle Pool 2.5 Breast ca. MDA-N 2.0 Spleen Pool 22.7Breast Pool 3.8 Thymus Pool 21.8 Trachea 3.9 CNS cancer (glio/astro) 0.2U87-MG Lung 3.6 CNS cancer (glio/astro) 6.2 U-118-MG Fetal Lung 10.1 CNScancer (neuro; met) SK-N-AS 0.0 Lung ca. NCI-N417 0.0 CNS cancer (astro)SF- 2.1 539 Lung ca. LX-1 0.0 CNS cancer (astro) 2.8 SNB-75 Lung ca.NCI-H146 0.0 CNS cancer (glio) SNB- 0.0 19 Lung ca. SHP-77 0.0 CNScancer (glio) SF- 21.9 295 Lung ca. A549 0.0 Brain (Amygdala) Pool 0.8Lung ca. NCI-H526 0.0 Brain (cerebellum) 0.8 Lung ca. NCI-H23 0.0 Brain(fetal) 0.1 Lung ca. NCI-H460 0.0 Brain (Hippocampus) 0.3 Pool Lung ca.HOP-62 0.8 Cerebral Cortex Pool 0.4 Lung ca. NCI-H522 0.0 Brain(Substantia nigra) 0.9 Pool Liver 0.1 Brain (Thalamus) Pool 1.6 FetalLiver 0.6 Brain (whole) 0.6 Liver ca. HepG2 0.0 Spinal Cord Pool 1.2Kidney Pool 10.7 Adrenal Gland 1.5 Fetal Kidney 3.3 Pituitary gland Pool0.1 Renal ca. 786-0 1.2 Salivary Gland 0.9 Renal ca. A498 1.5 Thyroid(female) 0.3 Renal ca. ACHN 0.0 Pancreatic ca. CAPAN2 1.4 Renal ca.UO-31 0.0 Pancreas Pool 2.9

[0685] TABLE GC Panel CNS_1.1 Rel. Rel. Exp. (%) Exp. (%) Ag6580,Ag6580, Run Run Tissue Name 274223227 Tissue Name 274223227 Cing Gyr 6.7BA17 PSP2 4.0 Depression2 Cing Gyr Depression 0.0 BA17 PSP 11.0 Cing GyrPSP2 0.0 BA17 24.5 Huntington's2 Cing Gyr PSP 7.3 BA17 10.0 Huntington'sCing Gyr 28.9 BA17 21.2 Huntington's2 Parkinson's2 Cing Gyr 63.3 BA17Parkinson's 78.5 Huntington's Cing Gyr 36.3 BA17 12.7 Parkinson's2Alzheimer's2 Cing Gyr Parkinson's 41.5 BA17 Control2 26.1 Cing Gyr 0.0BA17 Control 32.5 Alzheimer's2 Cing Gyr Alzheimer's 4.6 BA9 Depression23.8 Cing Gyr Control2 12.2 BA9 Depression 13.5 Cing Gyr Control 43.5 BA9PSP2 1.7 Temp Pole 14.7 BA9 PSP 0.0 Depression2 Temp Pole PSP2 0.0 BA915.2 Huntington's2 Temp Pole PSP 0.0 BA9 42.9 Huntington's Temp Pole50.0 BA9 Parkinson's2 0.0 Huntington's Temp Pole 0.0 BA9 Parkinson's 1.6Parkinson's2 Temp Pole 33.7 BA9 11.1 Parkinson's Alzheimer's2 Temp Pole1.7 BA9 Alzheimer's 0.0 Alzheimer's2 Temp Pole 0.0 BA9 Control2 54.7Alzheimer's Temp Pole Control2 5.6 BA9 Control 4.6 Temp Pole Control12.5 BA7 Depression 18.7 Glob Palladus 5.6 BA7 PSP2 0.0 Depression GlobPalladus PSP2 0.0 BA7 PSP 10.2 Glob Palladus PSP 0.0 BA7 57.8Huntington's2 Glob Palladus 3.1 BA7 36.9 Parkinson's2 Huntington's GlobPalladus 79.6 BA7 Parkinson's2 21.3 Parkinson's Glob Palladus 12.5 BA7Parkinson's 14.3 Alzheimer's2 Glob Palladus 13.4 BA7 0.0 Alzheimer'sAlzheimer's2 Glob Palladus 2.6 BA7 Control2 18.7 Control2 Glob PalladusControl 23.2 BA7 Control 18.3 Sub Nigra 13.2 BA4 Depression2 27.5Depression2 Sub Nigra Depression 45.1 BA4 Depression 8.6 Sub Nigra PSP22.1 BA4 PSP2 0.0 Sub Nigra 100.0 BA4 PSP 2.4 Huntington's2 Sub Nigia86.5 BA4 12.0 Huntington's Huntington's2 Sub Nigra 63.7 BA4 20.0Parkinson's2 Huntington's Sub Nigra 26.6 BA4 Parkinson's2 75.3Alzheimer's2 Sub Nigra Control2 1.6 BA4 Parkinson's 55.5 Sub NigraControl 77.4 BA4 0.0 Alzheimer's2 BA17 Depression2 43.5 BA4 Control214.2 BA17 Depression 29.1 BA4 Control 0.0

[0686] General_screening_panel_v1.6 Summary: Ag6580 Highest expressionof this gene is seen in a gastric cancer cell line (CT=28.8). Moderateexpression is also seen in brain and breast cancer cell lines, with lowexpression in melanoma and ovarian cancer cell lines. Modulation of thisgene product may be useful in the treatment of cancer.

[0687] Among tissues with metabolic function, this gene is expressed atlow but significant levels in adipose, adrenal gland, pancreas, andadult and fetal skeletal muscle and heart. This expression among thesetissues suggests that this gene product may play a role in normalneuroendocrine and metabolic function and that disregulated expressionof this gene may contribute to neuroendocrine disorders or metabolicdiseases, such as obesity and diabetes.

[0688] Panel CNS_(—)1.1 Summary: Ag6580 This gene is expressed at lowlevels in the CNS on this panel. Therefore, therapeutic modulation ofthe expression or function of this gene may be useful in the treatmentof neurological disorders, such as Alzheimer's disease, Parkinson'sdisease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0689] H. CG127897-01: Syntenin-2BETA

[0690] Expression of gene CG127897-01 was assessed using theprimer-probe set Ag4757, described in Table HA. TABLE HA Probe NameAg4757 Primers Sequences Length Start Position SEQ ID No Forward5′-gacaggatagtccagtggattg-3′ 22 266 113 ProbeTET-5′-atgcacaaggacagcacaagccat-3′-TAMRA 24 293 114 Reverse5′-gaagacctttcccttcttgatg-3′ 22 328 115

[0691] CNS_neurodegeneration_v1.0 Summary: Ag4757 Expression of theCG127897-01 gene is low/undetectable (CTs>35) across all of the sampleson this panel.

[0692] General_screening_panel_v1.4 Summary: Ag4757 Expression of theCG127897-01 gene is low/undetectable (CTs>35) across all of the sampleson this panel.

[0693] Panel 4.1D Summary: Ag4757 Expression of the CG127897-01 gene islow/undetectable (CTs>35) across all of the samples on this panel.

[0694] I. CG127936-01 and CG127936-02: PLK INTERACTING PROTEIN

[0695] Expression of gene CG127936-01 and full length physical cloneCG127936-02 was assessed using the primer-probe set Ag4770, described inTable IA. Results of the RTQ-PCR runs are shown in Tables IB and IC.Please note that CG127936-02 represents a full-length physical clone ofthe CG127936-01 gene, validating the prediction of the gene sequence.TABLE IA Probe Name Ag4770 Start SEQ ID Primers Sequences LengthPosition No Forward 5′-caagcctgtcttgttgctgt-3′ 20 528 116 ProbeTET-5′-tggcgcaaagctcaagaagtctgtaa-3′-TAMRA 26 558 117 Reverse5′-tttcctaaggtttggccaac-3′ 20 588 118

[0696] TABLE IB General_screening panel_v1.4 Rel. Exp. (%) Rel. Exp. (%)Ag4770, Ag4770, Run Run Tissue Name 222350146 Tissue Name 222350146Adipose 11.5 Renal ca. TK-10 23.7 Melanoma* 12.8 Bladder 35.6 Hs688(A).T Melanoma* 21.2 Gastric ca. (liver met.) NCI-N87 27.0 Hs688 (B).TMelanoma* M14 1.0 Gastric ca. KATO III 0.0 Melanoma* 21.3 Colon ca.SW-948 14.5 LOXIMVI Melanoma* SK- 12.2 Colon ca. SW480 53.2 MEL-5Squamous cell 7.1 Colon ca.* (SW480 met) 42.6 carcinoma SCC-4 SW620Testis Pool 27.9 Colon ca HT29 2.4 Prostate ca.* (bone met) PC-3 21.2Colon ca HCT-116 38.4 Prostate Pool 12.9 Colon ca CaCo-2 12.2 Placenta0.9 Colon cancer tissue 9.0 Uterus Pool 13.9 Colon ca SW1116 5.8 Ovarianca. OVCAR- 48.6 Colon ca Colo-205 3.1 3 Ovarian ca. SK-OV-3 44.1 Colonca. SW-48 5.0 Ovarian ca. OVCAR- 7.3 Colon Pool 35.4 4 Ovarian ca.OVCAR-5 30.8 Small Intestine Pool 33.0 Ovarian ca. IGROV-1 16.6 StomachPool 15.4 Ovarian ca. OVCAR- 13.6 Bone Marrow Pool 12.9 8 Ovary 20.3Fetal Heart 25.3 Breast ca. MCF-7 11.3 Heart Pool 15.1 Breast ca.MDA-MB- 8.0 Lymph Node Pool 46.3 231 Breast ca. BT 549 64.2 FetalSkeletal Muscle 7.7 Breast ca. T47D 51.1 Skeletal Muscle Pool 8.4 Breastca. MDA-N 0.0 Spleen Pool 10.7 Breast Pool 38.7 Thymus Pool 27.0 Trachea19.8 CNS cancer (glio/astro) 9.0 U87-MG Lung 14.5 CNS cancer(glio/astro) 89.5 U-118-MG Fetal Lung 69.7 CNS cancer (neuro;met) 55.5SK-N-AS Lung ca. NCI-N417 7.2 CNS cancer (astro) SF- 7.2 539 Lung ca.LX-1 46.3 CNS cancer (astro) 17.7 SNB-75 Lung ca. NCI-H146 46.3 CNScancer (glio) SNB- 16.4 19 Lung ca. SHP-77 100.0 CNS cancer (glio) SF-49.3 295 Lung ca. A549 17.3 Brain (Amygdala) Pool 6.8 Lung ca. NCI-H52610.4 Brain (cerebellum) 11.6 Lung ca. NCI-H23 41.2 Brain (fetal) 28.5Lung ca. NCI-H460 37.6 Brain (Hippocampus) 10.2 Pool Lung ca HOP-62 10.4Cerebral Cortex Pool 11.7 Lung ca NCI-H522 28.7 Brain (Substantia nigra)8.7 Pool Liver 0.4 Brain (Thalamus) Pool 18.7 Fetal Liver 15.3 Brain(whole) 9.0 Liver ca. HepG2 8.9 Spinal Cord Pool 10.9 Kidney Pool 49.7Adrenal Gland 8.1 Fetal Kidney 45.1 Pituitary gland Pool 13.3 Renal ca.786-0 25.0 Salivary Gland 6.4 Renal ca. A498 7.6 Thyroid (female) 14.4Renal ca. ACHN 19.6 Pancreatic ca. CAPAN2 6.8 Renal ca. UO-31 22.5Pancreas Pool 30.6

[0697] TABLE IC Panel 4.1D Rel. Rel. Exp. (%) Exp. (%) Ag4770, Ag4770,Run Run Tissue Name 204964145 Tissue Name 204964145 Secondary Th1 act29.7 HUVEC IL-1beta 21.3 Secondary Th2 act 26.8 HUVEC IFN gamma 24.7Secondary Tr1 act 16.6 HUVEC TNF alpha + IFN gamma 11.0 Secondary Th1rest 4.5 HUVEC TNF alpha + IL4 19.2 Secondary Th2 rest 12.8 HUVEC IL-1117.8 Secondary Tr1 rest 8.5 Lung Microvascular EC 54.7 none Primary Th1act 17.4 Lung Microvascular EC 28.9 TNFalpha + IL-1beta Primary Th2 act27.0 Microvascular Dermal EC 35.6 mone Primary Tr1 act 31.9Microsvasular Dermal EC 7.2 TNFalpha + IL-1beta Primary Th1 rest 8.8Bronchial epithelium 35.8 TNFalpha + IL1beta Primary Th2 rest 9.2 Smallairway epithelium 11.3 none Primary Tr1 rest 24.8 Small airwayepithelium 16.2 TNFalpha + IL-1beta CD45RA CD4 37.1 Coronery artery SMCrest 15.4 lymphocyte act CD45RO CD4 48.3 Coronery artery SMC 17.2lymphocyte act TNFalpha + IL-1beta CD8 lymphocyte act 33.4 Astrocytesrest 13.4 Secondary CD8 27.7 Astrocytes TNFalpha + IL- 6.2 lymphocyterest 1beta Secondary CD8 8.8 KU-812 (Basophil) rest 73.2 lymphocyte actCD4 lymphocyte none 18.6 KU-812 (Basophil) 100.0 PMA/ionomycin 2ryTh1/Th2/Tr1_anti- 17.3 CCD1106 (Keratinocytes) 30.8 CD95 CH11 none LAKcells rest 16.5 CCD1106 (Keratinocytes) 13.0 TNFalpha + IL-1beta LAKcells IL-2 33.2 Liver cirrhosis 14.2 LAK cells IL-2 + IL-12 9.5 NCI-H292none 47.6 LAK cells IL-2 + IFN 19.9 NCI-H292 IL-4 57.4 gamma LAK cellsIL-2 + IL-18 20.9 NCI-H292 IL-9 88.3 LAK cells 5.8 NCI-H292 IL-13 74.7PMA/ionomycin NK Cells IL-2 rest 33.9 NCI-H292 IFN gamma 80.1 Two WayMLR 3 day 14.4 HPAEC none 28.5 Two Way MLR 5 day 15.7 HPAEC TNF alpha +IL-1 18.3 beta Two Way MLR 7 day 5.8 Lung fibroblast none 32.5 PBMC rest4.5 Lung fibroblast TNF alpha + IL-1 beta 17.4 PBMC PWM 17.3 Lungfibroblast IL-4 16.7 PBMC PHA-L 31.2 Lung fibroblast IL-9 27.0 Ramos (Bcell) none 60.7 Lung fibroblast IL-13 17.7 Ramos (B cell) 74.7 Lungfibroblast IFN gamma 17.3 ionomycin B lymphocytes PWM 34.2 Dermalfibroblast CCD1070 37.1 rest B lymphocytes CD40L 17.4 Dermal fibroblastCCD1070 36.9 and IL-4 TNF alpha EOL-1 dbcAMP 27.5 Dermal fibroblastCCD1070 15.6 IL-1 beta EOL-I dbcAMP 7.7 Dermal fibroblast IFN 15.8PMA/ionomycin gamma Dendritic cells none 9.3 Dermal fibroblast IL-4 31.4Dendritic cells LPS 1.4 Dermal Fibroblasts rest 46.0 Dendritic cellsanti- 0.0 Neutrophils TNFa + LPS 0.9 CD40 Monocytes rest 1.7 Neutrophilsrest 1.9 Monocytes LPS 0.9 Colon 8.0 Macrophages rest 13.6 Lung 25.0Macrophages LPS 1.0 Thymus 57.0 HUVEC none 26.4 Kidney 80.1 HUVECstarved 21.2

[0698] General_screening_panel_v1.4 Summary: Ag4770 Highest expressionof the CG127936-01 gene is detected in lung cancer SHP-77 cell line(CT=29.9). Moderate levels of expression of this gene is also seen incluster of cancer cell lines derived from pancreatic, gastric, colon,lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma,melanoma and brain cancers. Thus, expression of this gene could be usedas a marker to detect the presence of these cancers. Furthermore,therapeutic modulation of the expression or function of this gene may beeffective in the treatment of pancreatic, gastric, colon, lung, liver,renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma andbrain cancers.

[0699] Among tissues with metabolic or endocrine function, this gene isexpressed at moderate levels in pancreas, adipose, adrenal gland,thyroid, pituitary gland, skeletal muscle, heart, liver and thegastrointestinal tract. Therefore, therapeutic modulation of theactivity of this gene may prove useful in the treatment ofendocrine/metabolically related diseases, such as obesity and diabetes.

[0700] Interestingly, this gene is expressed at much higher levels infetal (CT=32.2) when compared to adult liver (CT=40). This observationsuggests that expression of this gene can be used to distinguish fetalfrom adult liver. In addition, the relative overexpression of this genein fetal tissue suggests that the protein product may enhance livergrowth or development in the fetus and thus may also act in aregenerative capacity in the adult. Therefore, therapeutic modulation ofthe protein encoded by this gene could be useful in treatment of liverrelated diseases.

[0701] In addition, this gene is expressed at moderate levels in allregions of the central nervous system examined, including amygdala,hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex,and spinal cord. Therefore, therapeutic modulation of this gene productmay be useful in the treatment of central nervous system disorders suchas Alzheimer's disease, Parkinson's disease, epilepsy, multiplesclerosis, schizophrenia and depression.

[0702] Panel 4.1D Summary: Ag4770 Highest expression of the CG127936-01gene is detected in PMA/ionomycin treated basophils (CT=31.6). This geneis expressed at high to moderate levels in a wide range of cell types ofsignificance in the immune response in health and disease. These cellsinclude members of the T-cell, B-cell, endothelial cell,macrophage/monocyte, and peripheral blood mononuclear cell family, aswell as epithelial and fibroblast cell types from lung and skin, andnormal tissues represented by colon, lung, thymus and kidney. Thisubiquitous pattern of expression suggests that this gene product may beinvolved in homeostatic processes for these and other cell types andtissues. This pattern is in agreement with the expression profile inGeneral_screening_panel_v1.4 and also suggests a role for the geneproduct in cell survival and proliferation. Therefore, modulation of thegene product with a functional therapeutic may lead to the alteration offunctions associated with these cell types and lead to improvement ofthe symptoms of patients suffering from autoimmune and inflammatorydiseases such as asthma, allergies, inflammatory bowel disease, lupuserythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0703] J. CG127954-01: Novel Intracellular Protein

[0704] Expression of gene CG127954-01 was assessed using theprimer-probe set Ag4758, described in Table JA. Results of the RTQ-PCRruns are shown in Tables JB and JC. TABLE JA Probe Name Ag4758 Start SEQID Primers Sequences Length Position No Forward5′-acaaaccatggaagacttcaag-3′ 22 1047 119 ProbeTET-5′-ccagaagaatatcctttaactccagaaaca-3′-TAMRA 30 1069 120 Reverse5′-cttcccatttgttttcgtaaca-3′ 22 1105 121

[0705] TABLE JB CNS_neurodegeneration_v1.0 Rel. Rel. Exp. (%) Exp. (%)Ag4758, Ag4758, Run Run Tissue Name 224721732 Tissue Name 224721732 AD 1Hippo 15.0 Control (Path) 3 9.8 Temporal Ctx AD 2 Hippo 33.9 Control(Path) 4 45.4 Temporal Ctx AD 3 Hippo 14.0 AD 1 Occipital Ctx 25.5 AD 4Hippo 11.4 AD 2 Occipital Ctx 0.0 (Missing) AD 5 hippo 86.5 AD 3Occipital Ctx 12.3 AD 6 Hippo 100.0 AD 4 Occipital Ctx 21.5 Control 2Hippo 22.4 AD 5 Occipital Ctx 53.2 Control 4 Hippo 19.6 AD 6 OccipitalCtx 37.6 Control (Path) 3 14.9 Control 1 Occipital 8.5 Hippo Ctx AD 1Temporal Ctx 20.4 Control 2 Occipital 39.5 Ctx AD 2 Temporal Ctx 32.8Control 3 Occipital 20.9 Ctx AD 3 Temporal Ctx 10.6 Control 4 Occipital12.3 Ctx AD 4 Temporal Ctx 24.0 Control (Path) 1 78.5 Occipital Ctx AD 5Inf Temporal 78.5 Control (Path) 2 14.6 Ctx Occipital Ctx AD 5SupTemporal 49.7 Control (Path) 3 6.0 Ctx Occipital Ctx AD 6 InfTemporal 94.0 Control (Path) 4 23.3 Ctx Occipital Ctx AD 6 Sup Temporal90.8 Control 1 Parietal 9.0 Ctx Ctx Control 1 Temporal 11.2 Control 2Parietal 46.0 Ctx Ctx Control 2 Temporal 19.9 Control 3 Parietal 17.8Ctx Ctx Control 3 Temporal 12.9 Control (Path) 1 78.5 Ctx Parietal CtxControl 4 Temporal 11.3 Control (Path) 2 31.0 Ctx Parietal Ctx Control(Path) 1 62.0 Control (Path) 3 16.5 Temporal Ctx Parietal Ctx Control(Path) 2 30.8 Control (Path) 4 46.0 Temporal Ctx Parietal Ctx

[0706] TABLE JC General_screening_panel_v1.4 Rel. Exp. (%) Rel. Exp. (%)Ag4758, Run Ag4758, Run Tissue Name 223110462 Tissue Name 223110462Adipose 8.4 Renal ca. TK-10 10.7 Melanoma* 21.5 Bladder 17.9 Hs688(A).TMelanoma* 17.3 Gastric ca. (liver met.) 54.3 Hs688(B).T NCI-N87Melanoma* M14 1.1 Gastric ca. KATO III 16.0 Melanoma* 9.1 Colon ca.SW-948 1.1 LOXIMVI Melanoma* SK- 12.2 Colon ca. SW480 20.9 MEL-5Squamous cell 2.3 Colon ca.* (SW480 met) 11.6 carcinoma SCC-4 SW620Testis Pool 20.4 Colon ca. HT29 5.3 Prostate ca.* (bone 27.9 Colon ca.HCT-116 8.8 met) PC-3 Prostate Pool 8.2 Colon ca. CaCo-2 32.3 Placenta0.7 Colon cancer tissue 8.0 Uterus Pool 10.4 Colon ca. SW1116 1.4Ovarian ca. OVCAR-3 12.0 Colon ca. Colo-205 0.3 Ovarian ca. SK-OV-3 7.8Colon ca. SW-48 0.3 Ovarian ca. OVCAR-4 6.0 Colon Pool 24.0 Ovarian ca.OVCAR-5 16.2 Small Intestine Pool 24.3 Ovarian ca. IGROV-1 9.2 StomachPool 11.5 Ovarian ca. OVCAR-8 8.5 Bone Marrow Pool 9.0 Ovary 12.9 FetalHeart 4.1 Breast ca. MCF-7 3.7 Heart Pool 10.7 Breast ca. MDA-MB- 4.8Lymph Node Pool 30.6 231 Breast ca. BT 549 14.1 Fetal Skeletal Muscle4.3 Breast ca. T47D 30.6 Skeletal Muscle Pool 3.6 Breast ca. MDA-N 0.7Spleen Pool 4.9 Breast Pool 20.4 Thymus Pool 14.6 Trachea 14.4 CNScancer (glio/astro) 4.3 U87-MG Lung 15.0 CNS cancer (glio/astro) 12.4U-118-MG Fetal Lung 100.0 CNS cancer (neuro: met) 15.6 SK-N-AS Lung ca.NCI-N417 1.3 CNS cancer (astro) SF- 11.2 539 Lung ca. LX-1 3.7 CNScancer (astro) 29.9 SNB-75 Lung ca. NCI-H146 6.7 CNS cancer (glio) SNB-9.2 19 Lung ca. SHP-77 24.0 CNS cancer (glio) SF- 25.7 295 Lung ca. A5496.3 Brain (Amygdala) Pool 9.7 Lung ca. NCI-H526 4.5 Brain (cerebellum)14.9 Lung ca. NCI-H23 11.7 Brain (fetal) 13.7 Lung ca. NCI-H460 3.2Brain (Hippocampus) 19.5 Pool Lung ca. HOP-62 11.8 Cerebral Cortex Pool23.5 Lung ca. NCI-H522 16.5 Brain (Substantia nigra) 17.1 Pool Liver 0.0Brain (Thalamus) Pool 31.9 Fetal Liver 8.4 Brain (whole) 7.3 Liver ca.HepG2 5.6 Spinal Cord Pool 23.5 Kidney Pool 38.7 Adrenal Gland 1.5 FetalKidney 33.4 Pituitary gland Pool 5.1 Renal ca. 786-0 24.5 Salivary Gland1.3 Renal ca. A498 9.0 Thyroid (female) 8.7 Renal ca. ACHN 16.3Pancreatic ca. CAPAN2 6.9 Renal ca. UO-31 25.7 Pancreas Pool 24.1

[0707] CNS_neurodegeneration_v1.0 Summary: Ag4758 This panel does notshow differential expression of this gene in Alzheimer's disease.However, this profile confirms the expression of this gene at moderatelevels in the brain. Please see Panel 1.4 for discussion of this gene inthe central nervous system.

[0708] General_screening_panel_v1.4 Summary: Ag4758 This gene is widelyexpressed at low levels in this panel, with highest expression in fetallung (CT=30). In addition, this gene is expressed at much higher levelsin fetal lung tissue when compared to expression in the adultcounterpart (CT=33). Thus, expression of this gene may be used todifferentiate between the fetal and adult source of this tissue.

[0709] This gene is also expressed at low levels in the CNS, includingthe hippocampus, thalamus, substantia nigra, amygdala, cerebellum andcerebral cortex. Therefore, therapeutic modulation of the expression orfunction of this gene may be useful in the treatment of neurologicaldisorders, such as Alzheimer's disease, Parkinson's disease,schizophrenia, multiple sclerosis, stroke and epilepsy.

[0710] Panel 4.1D Summary: Ag4758 Expression of this gene islow/undetectable in all samples on this panel (CTs>35).

[0711] K. CG128132-01: RAL-A EXCHANGE FACTOR RALGPS2

[0712] Expression of gene CG128132-01 was assessed using theprimer-probe set Ag4760, described in Table KA. Results of the RTQ-PCRruns are shown in Tables KB, KC and KD. TABLE KA Probe Name Ag4760 StartSEQ ID Primers Sequences Length Position No Forward5′-agcttaaagatgacaccttgca-3′ 22 836 122 ProbeTET-5′-tgtcagatttaacatacatcgattcagca-3′-TAMRA 29 879 123 Reverse5′-ttctagaatgctgccagttgat-3′ 22 913 124

[0713] TABLE KB CNS_neurodegeneration_v1.0 Rel. Exp. (%) Rel. Exp. (%)Ag4760, Run Ag4760, Run Tissue Name 224721733 Tissue Name 224721733 AD 1Hippo 10.4 Control (Path) 3 2.0 Temporal Ctx AD 2 Hippo 32.5 Control(Path) 4 29.7 Temporal Ctx AD 3 Hippo 18.2 AD 1 Occipital Ctx 21.0 AD 4Hippo 4.3 AD 2 Occipital Ctx 0.0 (Missing) AD 5 Hippo 88.3 AD 3Occipital Ctx 5.8 AD 6 Hippo 100.0 AD 4 Occipital Ctx 8.3 Control 2Hippo 29.1 AD 5 Occipital Ctx 50.7 Control 4 Hippo 12.2 AD 6 OccipitalCtx 18.7 Control (Path) 3 5.4 Control 1 Occipital 2.9 Hippo Ctx AD 1Temporal Ctx 22.5 Control 2 Occipital 48.0 Ctx AD 2 Temporal Ctx 29.3Control 3 Occipital 11.6 Ctx AD 3 Temporal Ctx 7.1 Control 4 Occipital4.1 Ctx AD 4 Temporal Ctx 14.3 Control (Path) 1 73.7 Occipital Ctx AD 5Inf Temporal 73.7 Control (Path) 2 6.8 Ctx Occipital Ctx AD 5 SupTemporal 96.6 Control (Path) 3 1.9 Ctx Occipital Ctx AD 6 Inf Temporal46.0 Control (Path) 4 13.7 Ctx Occipital Ctx AD 6 Sup Temporal 46.0Control 1 Parietal 4.6 Ctx Ctx Control 1 Temporal 2.9 Control 2 Parietal49.7 Ctx Ctx Control 2 Temporal 30.8 Control 3 Parietal 11.3 Ctx CtxControl 3 Temporal 12.4 Control (Path) 1 46.0 Ctx Parietal Ctx Control 3Temporal 5.4 Control (Path) 2 20.4 Ctx Parietal Ctx Control (Path) 148.3 Control (Path) 3 2.9 Temporal Ctx Parietal Ctx Control (Path) 230.4 Control (Path) 4 20.2 Temporal Ctx Parietal Ctx

[0714] TABLE KC General_screening_panel_v1.4 Rel. Exp. (%) Rel. Exp. (%)Ag4760, Run Ag4760, Run Tissue Name 223110477 Tissue Name 223110477Adipose 0.0 Renal ca. TK-10 27.0 Melanoma* 27.5 Bladder 0.0 Hs688(A).TMelanoma* 16.0 Gastric ca. (liver met.) 42.6 Hs688(B).T NCI-N87Melanoma* M14 59.9 Gastric ca. KATO III 20.2 Melanoma* 4.8 Colon ca.SW-948 4.8 LOXIMVI Melanoma* SK- 27.2 Colon ca. SW480 24.1 MEL-5Squamous cell 14.3 Colon ca.* (SW480 met) 6.8 carcinoma SCC-4 SW620Testis Pool 36.6 Colon ca. HT29 15.3 Prostate ca.* (bone 60.7 Colon ca.HCT-116 21.3 met) PC-3 Prostate Pool 7.0 Colon ca. CaCo-2 34.9 Placenta0.9 Colon cancer tissue 13.0 Uterus Pool 3.8 Colon ca. SW1116 5.1Ovarian ca. OVCAR-3 36.9 Colon ca. Colo-205 3.6 Ovarian ca. SK-OV-3 54.0Colon ca. SW-48 4.9 Ovarian ca. OVCAR-4 30.1 Colon Pool 10.7 Ovarian ca.OVCAR-5 50.7 Small Intestine Pool 8.5 Ovarian ca. IGROV-1 10.2 StomachPool 6.9 Ovarian ca. OVCAR-8 9.2 Bone Marrow Pool 0.0 Ovary 4.3 FetalHeart 4.5 Breast ca. MCF-7 12.7 Heart Pool 2.6 Breast ca. MDA-MB-23135.4 Lymph Node Pool 11.1 Breast ca. BT 549 100.0 Fetal Skeletal Muscle5.8 Breast ca. T47D 85.9 Skeletal Muscle Pool 2.2 Breast ca. MDA-N 20.3Spleen Pool 25.9 Breast Pool 9.3 Thymus Pool 15.6 Trachea 9.5 CNS cancer(glio/astro) 14.0 U87-MG Lung 1.7 CNS cancer (glio/astro) 36.9 U-118-MGFetal Lung 7.3 CNS cancer (neuro: met) 0.3 SK-N-AS Lung ca. NCI-N417 0.0CNS cancer (astro) SF- 5.6 539 Lung ca. LX-1 17.1 CNS cancer (astro)51.1 SNB-75 Lung ca. NCI-H146 5.7 CNS cancer (glio) SNB- 10.6 19 Lungca. SHP-77 1.0 CNS cancer (glio) SF- 12.3 295 Lung ca. A549 28.5 Brain(Amygdala) Pool 0.0 Lung ca. NCI-H526 16.2 Brain (cerebellum) 0.0 Lungca. NCI-H23 15.3 Brain (fetal) 2.2 Lung ca. NCI-H460 2.1 Brain(Hippocampus) 0.2 Pool Lung ca. HOP-62 9.6 Cerebral Cortex Pool 0.6 Lungca. NCI-H522 32.8 Brain (Substantia nigra) 0.9 Pool Liver 0.6 Brain(Thalamus) Pool 1.4 Fetal Liver 21.5 Brain (whole) 0.5 Liver ca. HepG211.6 Spinal Cord Pool 4.7 Kidney Pool 11.2 Adrenal Gland 0.0 FetalKidney 10.7 Pituitary gland Pool 2.6 Renal ca. 786-0 29.5 Salivary Gland1.3 Renal ca. A498 4.7 Thyroid (female) 2.4 Renal ca. ACHN 19.6Pancreatic ca. CAPAN2 54.0 Renal ca. UO-31 20.0 Pancreas Pool 10.4

[0715] TABLE KD Panel 4.1D Rel. Exp. (%) Rel. Exp. (%) Ag4760, RunAg4760, Run Tissue Name 204408190 Tissue Name 204408190 Secondary Th1act 1.2 HUVEC IL-1beta 20.0 Secondary Th2 act 3.4 HUVEC IFN gamma 26.8Secondary Tr1 act 2.6 HUVEC TNF alpha + IFN 15.4 gamma Secondary Th1rest 1.6 HUVEC TNF alpha + IL4 13.9 Secondary Th2 rest 4.7 HUVEC IL-1115.9 Secondary Tr1 rest 1.3 Lung Microvascular EC 24.3 none Primary Th1act 1.5 Lung Microvascular EC 17.0 TNFalpha + IL-1beta Primary Th2 act2.2 Microvascular Dermal EC 24.1 none Primary Tr1 act 1.6 MicrosvasularDermal EC 10.6 TNFalpha + IL-1beta Primary Th1 rest 2.7 Bronchialepithelium 11.7 TNFalpha + IL1beta Primary Th2 rest 2.0 Small airwayepithelium 4.2 none Primary Tr1 rest 8.6 Small airway epithelium 10.2TNFalpha + IL-1beta CD45RA CD4 31.4 Coronery artery SMC rest 11.2lymphocyte act CD45RO CD4 8.6 Coronery artery SMC 11.0 lymphocyte actTNFalpha + IL-1beta CD8 lymphocyte act 3.2 Astrocytes rest 11.5Secondary CD8 2.1 Astrocytes TNFalpha + IL- 9.3 lymphocyte rest 1betaSecondary CD8 0.3 KU-812 (Basophil) rest 0.2 lymphocyte act CD4lymphocyte none 8.1 KU-812 (Basophil) 0.6 PMA/ionomycin 2ryTh1/Th2/Tr1_anti- 6.3 CCD1106 (Keratinocytes) 18.0 CD95 CH11 none LAKcells rest 16.3 CCD1106 (Keratinocytes) 22.1 TNFalpha + IL-1beta LAKcells IL-2 5.9 Liver cirrhosis 6.4 LAK cells IL-2 + IL-12 5.0 NCI-H292none 24.1 LAK cells IL-2 + IFN 3.5 NCI-H292 IL-4 40.6 gamma LAK cellsIL-2 + IL-18 6.3 NCI-H292 IL-9 65.1 LAK cells 11.6 NCI-H292 IL-13 42.0PMA/ionomycin NK Cells IL-2 rest 15.0 NCI-H292 IFN gamma 35.8 Two WayMLR 3 day 21.9 HPAEC none 10.6 Two Way MLR 5 day 7.1 HPAEC TNF alpha +IL-1 8.1 beta Two Way MLR 7 day 5.7 Lung fibroblast none 34.4 PBMC rest9.6 Lung fibroblast TNF alpha + 38.2 IL-1 beta PBMC PWM 4.2 Lungfibroblast IL-4 17.7 PBMC PHA-L 10.5 Lung fibroblast IL-9 21.8 Ramos (Bcell) none 84.7 Lung fibroblast IL-13 27.2 Ramos (B cell) 100.0 Lungfibroblast IFN gamma 52.5 ionomycin B lymphocytes PWM 17.6 Dermalfibroblast CCD1070 49.3 rest B lymphocytes CD40L 95.3 Dermal fibroblastCCD1070 37.9 and IL-4 TNF alpha EOL-1 dbcAMP 0.5 Dermal fibroblastCCD1070 38.7 IL-1 beta EOL-1 dbcAMP 0.5 Dermal fibroblast IFN 76.8PMA/ionomycin gamma Dendritic cells none 5.9 Dermal fibroblast IL-4 70.2Dendritic cells LPS 2.7 Dermal Fibroblasts rest 90.1 Dendritic cellsanti- 2.1 Neutrophils TNFa + LPS 3.1 CD40 Monocytes rest 5.6 Neutrophilsrest 18.4 Monocytes LPS 7.4 Colon 11.5 Macrophages rest 10.3 Lung 2.6Macrophages LPS 2.7 Thymus 36.6 HUVEC none 14.8 Kidney 20.9 HUVECstarved 32.5

[0716] CNS_neurodegeneration_v1.0 Summary: Ag4760 This panel confirmsthe expression of the CG128132-01 gene at low levels in the brains of anindependent group of individuals. However, no differential expression ofthis gene was detected between Alzheimer's diseased postmortem brainsand those of non-demented controls in this experiment. Please see Panel1.4 for a discussion of this gene in treatment of central nervous systemdisorders.

[0717] General_screening_panel_v1.4 Summary: Ag4760 Highest expressionof the CG128132-01 gene is detected in breast cancer BT 549 cell line(CT=25.9). Moderate to high levels of expression of this gene is alsoseen in cluster of cancer cell lines derived from pancreatic, gastric,colon, lung, liver, renal, breast, ovarian, prostate, squamous cellcarcinoma, melanoma and brain cancers. Thus, expression of this genecould be used as a marker to detect the presence of these cancers.Furthermore, therapeutic modulation of the expression or function ofthis gene may be effective in the treatment of pancreatic, gastric,colon, lung, liver, renal, breast, ovarian, prostate, squamous cellcarcinoma, melanoma and brain cancers.

[0718] Among tissues with metabolic or endocrine function, this gene isexpressed at moderate levels in pancreas, thyroid, pituitary gland,skeletal muscle, heart, liver and the gastrointestinal tract. Therefore,therapeutic modulation of the activity of this gene may prove useful inthe treatment of endocrine/metabolically related diseases, such asobesity and diabetes.

[0719] Interestingly, this gene is expressed at much higher levels infetal (CT=28) when compared to adult liver (CT=33). This observationsuggests that expression of this gene can be used to distinguish fetalfrom adult liver. In addition, the relative overexpression of this genein fetal tissue suggests that the protein product may enhance livergrowth or development in the fetus and thus may also act in aregenerative capacity in the adult. Therefore, therapeutic modulation ofthe protein encoded by this gene could be useful in treatment of liverrelated diseases.

[0720] In addition, this gene is expressed at moderate to low levels inall regions of the central nervous system examined, including amygdala,hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex,and spinal cord. Therefore, therapeutic modulation of this gene productmay be useful in the treatment of central nervous system disorders suchas Alzheimer's disease, Parkinson's disease, epilepsy, multiplesclerosis, schizophrenia and depression.

[0721] Panel 4.1D Summary: Ag4760 Highest expression of the CG128132-01gene is detected in ionomycin treated basophils (CT=28.9). This gene isexpressed at low to moderate levels in a wide range of cell types ofsignificance in the immune response in health and disease. These cellsinclude members of the T-cell, B-cell, endothelial cell,macrophage/monocyte, and peripheral blood mononuclear cell family, aswell as epithelial and fibroblast cell types from lung and skin, andnormal tissues represented by colon, lung, thymus and kidney. Thisubiquitous pattern of expression suggests that this gene product may beinvolved in homeostatic processes for these and other cell types andtissues. This pattern is in agreement with the expression profile inGeneral_screening_panel_v1.4 and also suggests a role for the geneproduct in cell survival and proliferation. Therefore, modulation of thegene product with a functional therapeutic may lead to the alteration offunctions associated with these cell types and lead to improvement ofthe symptoms of patients suffering from autoimmune and inflammatorydiseases such as asthma, allergies, inflammatory bowel disease, lupuserythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0722] L. CG128219-01: Adenosine-deaminase (Editase)

[0723] Expression of gene CG128219-01 was assessed using theprimer-probe set Ag4773, described in Table LA.

1 191 1 829 DNA Homo sapiens CDS (43)..(378) 1 gtccttggag gccagaggggactctgagca tcggaaagca gg atg cct ggt ttg 54 Met Pro Gly Leu 1 ctt ttatgt gaa ccg aca gag ctt tac aac atc ctg aat cag gcc aca 102 Leu Leu CysGlu Pro Thr Glu Leu Tyr Asn Ile Leu Asn Gln Ala Thr 5 10 15 20 aaa ctctcc aga tta aca gac ccc aac tat ctc tgt tta ttg gat gtc 150 Lys Leu SerArg Leu Thr Asp Pro Asn Tyr Leu Cys Leu Leu Asp Val 25 30 35 cgt tcc aaatgg gag tat gac gaa agc cat gtg atc act gcc ctt cga 198 Arg Ser Lys TrpGlu Tyr Asp Glu Ser His Val Ile Thr Ala Leu Arg 40 45 50 gtg aag aag aaaaat aat gaa tat ctt ctc ccg gaa tct gtg gac ctg 246 Val Lys Lys Lys AsnAsn Glu Tyr Leu Leu Pro Glu Ser Val Asp Leu 55 60 65 gag tgt gtg aag tactgc gtg gtg tat gat aac aac agc agc acc ctg 294 Glu Cys Val Lys Tyr CysVal Val Tyr Asp Asn Asn Ser Ser Thr Leu 70 75 80 gag ata ctc tta aaa gatgat gat gat gat tca gac tct gat ggt gat 342 Glu Ile Leu Leu Lys Asp AspAsp Asp Asp Ser Asp Ser Asp Gly Asp 85 90 95 100 ggc aaa gga act gga tgcatt tca gcc ata ccc cat tgaaatcgtg 388 Gly Lys Gly Thr Gly Cys Ile SerAla Ile Pro His 105 110 ccagggaagg tcttcgttgg caatttcagt caagcctgtgaccccaagat tcagaaggac 448 ttgaaaatca aagcccatgt caatgtctcc atggatacagggcccttttt tgcaggcgat 508 gctgacaagc ttctgcacat ccggatagaa gattccccggaagcccagat tcttcccttc 568 ttacgccaca tgtgtcactt cattgggtat cagccgcagttgtgccgcca tcatagccta 628 cctcatgtat agtaacgagc agaccttgca gaggtcctgggcctatgtca agaagtgcaa 688 aaacaacatg tgtccaaatc ggggattggt gagccagctgctggaatggg agaagactat 748 ccttggagat tccatcacaa acatcatgga tccgctctactgatcttctc cgaggcccac 808 cgaagggtac tgaagagcct c 829 2 112 PRT Homosapiens 2 Met Pro Gly Leu Leu Leu Cys Glu Pro Thr Glu Leu Tyr Asn IleLeu 1 5 10 15 Asn Gln Ala Thr Lys Leu Ser Arg Leu Thr Asp Pro Asn TyrLeu Cys 20 25 30 Leu Leu Asp Val Arg Ser Lys Trp Glu Tyr Asp Glu Ser HisVal Ile 35 40 45 Thr Ala Leu Arg Val Lys Lys Lys Asn Asn Glu Tyr Leu LeuPro Glu 50 55 60 Ser Val Asp Leu Glu Cys Val Lys Tyr Cys Val Val Tyr AspAsn Asn 65 70 75 80 Ser Ser Thr Leu Glu Ile Leu Leu Lys Asp Asp Asp AspAsp Ser Asp 85 90 95 Ser Asp Gly Asp Gly Lys Gly Thr Gly Cys Ile Ser AlaIle Pro His 100 105 110 3 1188 DNA Homo sapiens CDS (151)..(1038) 3agtgatggct tgtggattca agcctaggtt tgacagatct ggaatgtgtg ctcctattcc 60tccgcagtct ggcctgtctg ctttctgtct tctttgccag caatgtccag gcactgtaag 120gtgggccgtt agcttcctgg gttcaggtaa atg tct tcc agt aac ccc tgc ttc 174 MetSer Ser Ser Asn Pro Cys Phe 1 5 ccc tgc tcc ccg aca ggt aag ttc gag gatcgg gaa gac cac gtc ccc 222 Pro Cys Ser Pro Thr Gly Lys Phe Glu Asp ArgGlu Asp His Val Pro 10 15 20 aag ttg gag caa ata aac agc acg agg atc ctgagc agc cag aac ttc 270 Lys Leu Glu Gln Ile Asn Ser Thr Arg Ile Leu SerSer Gln Asn Phe 25 30 35 40 acc ctc acc aag aag gag ctg ctg agc aca gagctg ctg ctc ctg gag 318 Thr Leu Thr Lys Lys Glu Leu Leu Ser Thr Glu LeuLeu Leu Leu Glu 45 50 55 gcc ttc agc tgg aac ctc tgc ctg ccc acg cct gcccac ttc ctg gac 366 Ala Phe Ser Trp Asn Leu Cys Leu Pro Thr Pro Ala HisPhe Leu Asp 60 65 70 tac tac ctc ttg gcc tcc gtc agc cag aag gac cac cactgc cac acc 414 Tyr Tyr Leu Leu Ala Ser Val Ser Gln Lys Asp His His CysHis Thr 75 80 85 tgg ccc acc acc tgc ccc cgc aag acc aaa gag tgc ctc aaggag tat 462 Trp Pro Thr Thr Cys Pro Arg Lys Thr Lys Glu Cys Leu Lys GluTyr 90 95 100 gcc cat tac ttc cta gag gtc acc ctg caa gtc gct gcg gcctgt gtt 510 Ala His Tyr Phe Leu Glu Val Thr Leu Gln Val Ala Ala Ala CysVal 105 110 115 120 ggg gcc tcc agg att tgc ctg cag ctt tct ccc tac tggacc aga gac 558 Gly Ala Ser Arg Ile Cys Leu Gln Leu Ser Pro Tyr Trp ThrArg Asp 125 130 135 ctg cag agg atc tca agc tat tcc ctg gag cac ctc agcacg tgt att 606 Leu Gln Arg Ile Ser Ser Tyr Ser Leu Glu His Leu Ser ThrCys Ile 140 145 150 gaa atc ctg ctg gtg gtg tat gac aac gtc ctc aag gatgcc gta gcc 654 Glu Ile Leu Leu Val Val Tyr Asp Asn Val Leu Lys Asp AlaVal Ala 155 160 165 gtc aag agc cag gcc ttg gca atg gtg ccc ggc aca cccccc acc ccc 702 Val Lys Ser Gln Ala Leu Ala Met Val Pro Gly Thr Pro ProThr Pro 170 175 180 act caa gtg ctg ttc cag cca cca gcc tac ccg gcc ctcggc cag cca 750 Thr Gln Val Leu Phe Gln Pro Pro Ala Tyr Pro Ala Leu GlyGln Pro 185 190 195 200 gcg acc acc ctg gca cag ttc cag acc ccc gtg caggac cta tgc ttg 798 Ala Thr Thr Leu Ala Gln Phe Gln Thr Pro Val Gln AspLeu Cys Leu 205 210 215 gcc tat cgg gac tcc ttg cag gcc cac cgt tca gggagc ctg ctc tcg 846 Ala Tyr Arg Asp Ser Leu Gln Ala His Arg Ser Gly SerLeu Leu Ser 220 225 230 ggg agt aca ggc tca tcc ctc cac acc ccg tac caaccg ctg cag ccc 894 Gly Ser Thr Gly Ser Ser Leu His Thr Pro Tyr Gln ProLeu Gln Pro 235 240 245 ttg gat atg tgt ccc gtg ccc gtc cct gca tcc cttagc atg cat atg 942 Leu Asp Met Cys Pro Val Pro Val Pro Ala Ser Leu SerMet His Met 250 255 260 gcc att gca gct gag ccc agg cac tgc ctc gcc accacc tat gga agc 990 Ala Ile Ala Ala Glu Pro Arg His Cys Leu Ala Thr ThrTyr Gly Ser 265 270 275 280 agc tac ttc agt ggg agc cac atg ttc ccc accggc tgc ttt gac aga 1038 Ser Tyr Phe Ser Gly Ser His Met Phe Pro Thr GlyCys Phe Asp Arg 285 290 295 taggccacct ccagacctca cgaggaagcc ttggagatgtgggcagagga agaggacact 1098 gaagaggaga gctcagccaa gtgaggcagc aggaggccatccctgaagag ccttggaacg 1158 tggagggtct gtgctccttt taaataaaac 1188 4 296PRT Homo sapiens 4 Met Ser Ser Ser Asn Pro Cys Phe Pro Cys Ser Pro ThrGly Lys Phe 1 5 10 15 Glu Asp Arg Glu Asp His Val Pro Lys Leu Glu GlnIle Asn Ser Thr 20 25 30 Arg Ile Leu Ser Ser Gln Asn Phe Thr Leu Thr LysLys Glu Leu Leu 35 40 45 Ser Thr Glu Leu Leu Leu Leu Glu Ala Phe Ser TrpAsn Leu Cys Leu 50 55 60 Pro Thr Pro Ala His Phe Leu Asp Tyr Tyr Leu LeuAla Ser Val Ser 65 70 75 80 Gln Lys Asp His His Cys His Thr Trp Pro ThrThr Cys Pro Arg Lys 85 90 95 Thr Lys Glu Cys Leu Lys Glu Tyr Ala His TyrPhe Leu Glu Val Thr 100 105 110 Leu Gln Val Ala Ala Ala Cys Val Gly AlaSer Arg Ile Cys Leu Gln 115 120 125 Leu Ser Pro Tyr Trp Thr Arg Asp LeuGln Arg Ile Ser Ser Tyr Ser 130 135 140 Leu Glu His Leu Ser Thr Cys IleGlu Ile Leu Leu Val Val Tyr Asp 145 150 155 160 Asn Val Leu Lys Asp AlaVal Ala Val Lys Ser Gln Ala Leu Ala Met 165 170 175 Val Pro Gly Thr ProPro Thr Pro Thr Gln Val Leu Phe Gln Pro Pro 180 185 190 Ala Tyr Pro AlaLeu Gly Gln Pro Ala Thr Thr Leu Ala Gln Phe Gln 195 200 205 Thr Pro ValGln Asp Leu Cys Leu Ala Tyr Arg Asp Ser Leu Gln Ala 210 215 220 His ArgSer Gly Ser Leu Leu Ser Gly Ser Thr Gly Ser Ser Leu His 225 230 235 240Thr Pro Tyr Gln Pro Leu Gln Pro Leu Asp Met Cys Pro Val Pro Val 245 250255 Pro Ala Ser Leu Ser Met His Met Ala Ile Ala Ala Glu Pro Arg His 260265 270 Cys Leu Ala Thr Thr Tyr Gly Ser Ser Tyr Phe Ser Gly Ser His Met275 280 285 Phe Pro Thr Gly Cys Phe Asp Arg 290 295 5 1015 DNA Homosapiens CDS (24)..(944) 5 gttagcttcc tgggttcagg taa atg tct tcc agt aacccc tgc ttc ccc tgc 53 Met Ser Ser Ser Asn Pro Cys Phe Pro Cys 1 5 10tcc ccg aca ggt aag ttc gag gat cgg gaa gac cac gtc ccc aag ttg 101 SerPro Thr Gly Lys Phe Glu Asp Arg Glu Asp His Val Pro Lys Leu 15 20 25 gagcaa ata aac agc acg agg atc ctg agc agc cag aac ttc acc ctc 149 Glu GlnIle Asn Ser Thr Arg Ile Leu Ser Ser Gln Asn Phe Thr Leu 30 35 40 acc aagaag gag ctg ctg agc aca gag ctg ctg ctc ctg gag gcc ttc 197 Thr Lys LysGlu Leu Leu Ser Thr Glu Leu Leu Leu Leu Glu Ala Phe 45 50 55 agc tgg aacctc tgc ctg ccc acg cct gcc cac ttc ctg gac tac tac 245 Ser Trp Asn LeuCys Leu Pro Thr Pro Ala His Phe Leu Asp Tyr Tyr 60 65 70 ctc ttg gcc tccgtc agc cag aag gac cac cac tgc cac acc tgg ccc 293 Leu Leu Ala Ser ValSer Gln Lys Asp His His Cys His Thr Trp Pro 75 80 85 90 acc acc tgc ccccgc aag acc aaa gag tgc ctc aag gag tat gcc cat 341 Thr Thr Cys Pro ArgLys Thr Lys Glu Cys Leu Lys Glu Tyr Ala His 95 100 105 tac ttc cta gaggtc acc ctg caa gat cac ata ttc tac aaa ttc cag 389 Tyr Phe Leu Glu ValThr Leu Gln Asp His Ile Phe Tyr Lys Phe Gln 110 115 120 cct tct gtg gtcgct gcg gcc tgt gtt ggg gcc tcc agg att tgc ctg 437 Pro Ser Val Val AlaAla Ala Cys Val Gly Ala Ser Arg Ile Cys Leu 125 130 135 cag ctt tct ccctac tgg acc aga gac ctg cag agg atc tca agc tat 485 Gln Leu Ser Pro TyrTrp Thr Arg Asp Leu Gln Arg Ile Ser Ser Tyr 140 145 150 tcc ctg gag cacctc agc acg tgt att gaa atc ctg ctg gta gtg tat 533 Ser Leu Glu His LeuSer Thr Cys Ile Glu Ile Leu Leu Val Val Tyr 155 160 165 170 gac aac gtcctc aag gat gcc gta gcc gtc aag agc cag gcc ttg gca 581 Asp Asn Val LeuLys Asp Ala Val Ala Val Lys Ser Gln Ala Leu Ala 175 180 185 atg gtg cccggc aca ccc ccc acc ccc act caa gtg ctg ttc cag cca 629 Met Val Pro GlyThr Pro Pro Thr Pro Thr Gln Val Leu Phe Gln Pro 190 195 200 cca gcc tacccg gcc ctc ggc cag cca gcg acc acc ctg gca cag ttc 677 Pro Ala Tyr ProAla Leu Gly Gln Pro Ala Thr Thr Leu Ala Gln Phe 205 210 215 cag acc cccgtg cag gac cta tgc ttg gcc tat cgg gac tcc ttg cag 725 Gln Thr Pro ValGln Asp Leu Cys Leu Ala Tyr Arg Asp Ser Leu Gln 220 225 230 gcc cac cgttca ggg agc ctg ctc tcg ggg agt aca ggc tca tcc ctc 773 Ala His Arg SerGly Ser Leu Leu Ser Gly Ser Thr Gly Ser Ser Leu 235 240 245 250 cac accccg tac caa ccg ctg cag ccc ttg gat atg tgt ccc gtg ccc 821 His Thr ProTyr Gln Pro Leu Gln Pro Leu Asp Met Cys Pro Val Pro 255 260 265 gtc cctgca tcc ctt agc atg cat atg gcc att gca gct gag ccc agg 869 Val Pro AlaSer Leu Ser Met His Met Ala Ile Ala Ala Glu Pro Arg 270 275 280 cac tgcctc gcc acc acc tat gga agc agc tac ttc agt ggg agc cac 917 His Cys LeuAla Thr Thr Tyr Gly Ser Ser Tyr Phe Ser Gly Ser His 285 290 295 atg ttcccc acc ggc tgc ttt gac aga taggccacct ccagacctca 964 Met Phe Pro ThrGly Cys Phe Asp Arg 300 305 cgaggaagcc ttggagatgt gggcagagga agaggacactgaagaggaga g 1015 6 307 PRT Homo sapiens 6 Met Ser Ser Ser Asn Pro CysPhe Pro Cys Ser Pro Thr Gly Lys Phe 1 5 10 15 Glu Asp Arg Glu Asp HisVal Pro Lys Leu Glu Gln Ile Asn Ser Thr 20 25 30 Arg Ile Leu Ser Ser GlnAsn Phe Thr Leu Thr Lys Lys Glu Leu Leu 35 40 45 Ser Thr Glu Leu Leu LeuLeu Glu Ala Phe Ser Trp Asn Leu Cys Leu 50 55 60 Pro Thr Pro Ala His PheLeu Asp Tyr Tyr Leu Leu Ala Ser Val Ser 65 70 75 80 Gln Lys Asp His HisCys His Thr Trp Pro Thr Thr Cys Pro Arg Lys 85 90 95 Thr Lys Glu Cys LeuLys Glu Tyr Ala His Tyr Phe Leu Glu Val Thr 100 105 110 Leu Gln Asp HisIle Phe Tyr Lys Phe Gln Pro Ser Val Val Ala Ala 115 120 125 Ala Cys ValGly Ala Ser Arg Ile Cys Leu Gln Leu Ser Pro Tyr Trp 130 135 140 Thr ArgAsp Leu Gln Arg Ile Ser Ser Tyr Ser Leu Glu His Leu Ser 145 150 155 160Thr Cys Ile Glu Ile Leu Leu Val Val Tyr Asp Asn Val Leu Lys Asp 165 170175 Ala Val Ala Val Lys Ser Gln Ala Leu Ala Met Val Pro Gly Thr Pro 180185 190 Pro Thr Pro Thr Gln Val Leu Phe Gln Pro Pro Ala Tyr Pro Ala Leu195 200 205 Gly Gln Pro Ala Thr Thr Leu Ala Gln Phe Gln Thr Pro Val GlnAsp 210 215 220 Leu Cys Leu Ala Tyr Arg Asp Ser Leu Gln Ala His Arg SerGly Ser 225 230 235 240 Leu Leu Ser Gly Ser Thr Gly Ser Ser Leu His ThrPro Tyr Gln Pro 245 250 255 Leu Gln Pro Leu Asp Met Cys Pro Val Pro ValPro Ala Ser Leu Ser 260 265 270 Met His Met Ala Ile Ala Ala Glu Pro ArgHis Cys Leu Ala Thr Thr 275 280 285 Tyr Gly Ser Ser Tyr Phe Ser Gly SerHis Met Phe Pro Thr Gly Cys 290 295 300 Phe Asp Arg 305 7 1534 DNA Homosapiens CDS (151)..(1299) 7 aagcatggtt aaatctggta gatggagagc tcaggaaaagcggccatgag ctttcagcac 60 aattagtcct gacccttagg ggacacccta agggaagatgagtcccagga ctaaccaggg 120 gtgtgggcat ccctgtgttt aaaattccag atg ggc accaca cct tcc aaa ccg 174 Met Gly Thr Thr Pro Ser Lys Pro 1 5 gac act ccctta aga tgt atc ctg aat aac tgg gac aaa ttc gac cct 222 Asp Thr Pro LeuArg Cys Ile Leu Asn Asn Trp Asp Lys Phe Asp Pro 10 15 20 gaa acc tta aaaaag aag cag cta att ttc ttc tgt acc act gcc tgg 270 Glu Thr Leu Lys LysLys Gln Leu Ile Phe Phe Cys Thr Thr Ala Trp 25 30 35 40 cca cag tat tcctta caa aat gga gaa act tgg ccc cct gag gga tgt 318 Pro Gln Tyr Ser LeuGln Asn Gly Glu Thr Trp Pro Pro Glu Gly Cys 45 50 55 att aat tat aac accctt cta caa cta gct ctt ttc tgt aag cag gaa 366 Ile Asn Tyr Asn Thr LeuLeu Gln Leu Ala Leu Phe Cys Lys Gln Glu 60 65 70 ggt aaa tgg agt gaa gtccct tac gta cag gct ttc ttt gcc ctt ctt 414 Gly Lys Trp Ser Glu Val ProTyr Val Gln Ala Phe Phe Ala Leu Leu 75 80 85 gac aat act gcc ctg tgc caagcc tgc gag ctt tgc cca aat gac aga 462 Asp Asn Thr Ala Leu Cys Gln AlaCys Glu Leu Cys Pro Asn Asp Arg 90 95 100 ggc cca caa tta cct cca tattca ggg cct ctt ccc tca gcc cca ctc 510 Gly Pro Gln Leu Pro Pro Tyr SerGly Pro Leu Pro Ser Ala Pro Leu 105 110 115 120 tcc tcc tgc act gac tctcct cca tct ggc ctc act gaa gtg tta aag 558 Ser Ser Cys Thr Asp Ser ProPro Ser Gly Leu Thr Glu Val Leu Lys 125 130 135 gca aaa tgg aaa gag aacgta aac tcc gag agc cag gca ccc gaa cta 606 Ala Lys Trp Lys Glu Asn ValAsn Ser Glu Ser Gln Ala Pro Glu Leu 140 145 150 tgt ccc tta caa aca gtagga gga gaa ttt ggg cgc att cac atg cat 654 Cys Pro Leu Gln Thr Val GlyGly Glu Phe Gly Arg Ile His Met His 155 160 165 gcc ccc ttc tca ctc tcaaat tta aaa caa ata aag gca gat tta ggg 702 Ala Pro Phe Ser Leu Ser AsnLeu Lys Gln Ile Lys Ala Asp Leu Gly 170 175 180 aaa ttc ttg gat gat cctgat aac cat ata cat gtc ctg caa gga tta 750 Lys Phe Leu Asp Asp Pro AspAsn His Ile His Val Leu Gln Gly Leu 185 190 195 200 gag cag tcc ttt gatcta aca tgg aga gat atc atg tta ctt ctt gat 798 Glu Gln Ser Phe Asp LeuThr Trp Arg Asp Ile Met Leu Leu Leu Asp 205 210 215 cag acc tta agt cctact gaa aaa aaa gca gct tta gca gca gcc cag 846 Gln Thr Leu Ser Pro ThrGlu Lys Lys Ala Ala Leu Ala Ala Ala Gln 220 225 230 caa ttt agg gat cgatgg tac ctt ggc cag gta aac aat cca ttg atg 894 Gln Phe Arg Asp Arg TrpTyr Leu Gly Gln Val Asn Asn Pro Leu Met 235 240 245 gcc ttg gag gag agggaa aaa ttg ccc aca ggg gaa cag gca gtc ccc 942 Ala Leu Glu Glu Arg GluLys Leu Pro Thr Gly Glu Gln Ala Val Pro 250 255 260 act gta aat cct tattgg gat act gac tca gat cat gga gat tgg agc 990 Thr Val Asn Pro Tyr TrpAsp Thr Asp Ser Asp His Gly Asp Trp Ser 265 270 275 280 cac agg cat ttgcta act tgc att tta aaa ggg ttg agg aag act agg 1038 His Arg His Leu LeuThr Cys Ile Leu Lys Gly Leu Arg Lys Thr Arg 285 290 295 aga aag cct atgaac tac tca atg cta tcc acc att acc cag gga aaa 1086 Arg Lys Pro Met AsnTyr Ser Met Leu Ser Thr Ile Thr Gln Gly Lys 300 305 310 gaa gaa aat ccctca gcc ttt cta gaa atg ctg cgg gag gct cta aga 1134 Glu Glu Asn Pro SerAla Phe Leu Glu Met Leu Arg Glu Ala Leu Arg 315 320 325 agg cac acc cccgta act ccg gat tcc ctg gaa ggc caa ctt att cta 1182 Arg His Thr Pro ValThr Pro Asp Ser Leu Glu Gly Gln Leu Ile Leu 330 335 340 aag gat aaa cttatc acc cta aga agc ggc cga tat tgg gag aaa act 1230 Lys Asp Lys Leu IleThr Leu Arg Ser Gly Arg Tyr Trp Glu Lys Thr 345 350 355 360 cca aag gtctgc ctt agg ccc aga aca aag ctt gga ggc att att aaa 1278 Pro Lys Val CysLeu Arg Pro Arg Thr Lys Leu Gly Gly Ile Ile Lys 365 370 375 cct gcc aacctc gtt gtt cta taacagggac caagaggaac aggccaaaat 1329 Pro Ala Asn LeuVal Val Leu 380 ggaaaagcaa gataagagaa aggctgcagc cttagtcttg gctctcagacaggcagacct 1389 tggtggctca gagggaacca aaagaggagc aggccaattg cctagtagggcttgttatca 1449 gtgcggtttg caaggacact ttaaaaaaga ttgtccaact agaaacaaactgccccctcg 1509 cccatgtcca atatgccaag gcaat 1534 8 383 PRT Homo sapiens8 Met Gly Thr Thr Pro Ser Lys Pro Asp Thr Pro Leu Arg Cys Ile Leu 1 5 1015 Asn Asn Trp Asp Lys Phe Asp Pro Glu Thr Leu Lys Lys Lys Gln Leu 20 2530 Ile Phe Phe Cys Thr Thr Ala Trp Pro Gln Tyr Ser Leu Gln Asn Gly 35 4045 Glu Thr Trp Pro Pro Glu Gly Cys Ile Asn Tyr Asn Thr Leu Leu Gln 50 5560 Leu Ala Leu Phe Cys Lys Gln Glu Gly Lys Trp Ser Glu Val Pro Tyr 65 7075 80 Val Gln Ala Phe Phe Ala Leu Leu Asp Asn Thr Ala Leu Cys Gln Ala 8590 95 Cys Glu Leu Cys Pro Asn Asp Arg Gly Pro Gln Leu Pro Pro Tyr Ser100 105 110 Gly Pro Leu Pro Ser Ala Pro Leu Ser Ser Cys Thr Asp Ser ProPro 115 120 125 Ser Gly Leu Thr Glu Val Leu Lys Ala Lys Trp Lys Glu AsnVal Asn 130 135 140 Ser Glu Ser Gln Ala Pro Glu Leu Cys Pro Leu Gln ThrVal Gly Gly 145 150 155 160 Glu Phe Gly Arg Ile His Met His Ala Pro PheSer Leu Ser Asn Leu 165 170 175 Lys Gln Ile Lys Ala Asp Leu Gly Lys PheLeu Asp Asp Pro Asp Asn 180 185 190 His Ile His Val Leu Gln Gly Leu GluGln Ser Phe Asp Leu Thr Trp 195 200 205 Arg Asp Ile Met Leu Leu Leu AspGln Thr Leu Ser Pro Thr Glu Lys 210 215 220 Lys Ala Ala Leu Ala Ala AlaGln Gln Phe Arg Asp Arg Trp Tyr Leu 225 230 235 240 Gly Gln Val Asn AsnPro Leu Met Ala Leu Glu Glu Arg Glu Lys Leu 245 250 255 Pro Thr Gly GluGln Ala Val Pro Thr Val Asn Pro Tyr Trp Asp Thr 260 265 270 Asp Ser AspHis Gly Asp Trp Ser His Arg His Leu Leu Thr Cys Ile 275 280 285 Leu LysGly Leu Arg Lys Thr Arg Arg Lys Pro Met Asn Tyr Ser Met 290 295 300 LeuSer Thr Ile Thr Gln Gly Lys Glu Glu Asn Pro Ser Ala Phe Leu 305 310 315320 Glu Met Leu Arg Glu Ala Leu Arg Arg His Thr Pro Val Thr Pro Asp 325330 335 Ser Leu Glu Gly Gln Leu Ile Leu Lys Asp Lys Leu Ile Thr Leu Arg340 345 350 Ser Gly Arg Tyr Trp Glu Lys Thr Pro Lys Val Cys Leu Arg ProArg 355 360 365 Thr Lys Leu Gly Gly Ile Ile Lys Pro Ala Asn Leu Val ValLeu 370 375 380 9 1287 DNA Homo sapiens CDS (7)..(1278) 9 gccctg atg gagcac ctt gtt ccc acg gtg gac tat tac ccc gat agg 48 Met Glu His Leu ValPro Thr Val Asp Tyr Tyr Pro Asp Arg 1 5 10 acg tac atc ttc acc ttt ctcctg agc tcc cgg gtc ttt atg ccc cct 96 Thr Tyr Ile Phe Thr Phe Leu LeuSer Ser Arg Val Phe Met Pro Pro 15 20 25 30 cat gac ctg ctg gcc cgc gtgggg cag atc tgc gtg gag cag aag cag 144 His Asp Leu Leu Ala Arg Val GlyGln Ile Cys Val Glu Gln Lys Gln 35 40 45 cag ctg gaa gcc ggg cct gaa aagcag gcc aag ctg aag tct ttc tca 192 Gln Leu Glu Ala Gly Pro Glu Lys GlnAla Lys Leu Lys Ser Phe Ser 50 55 60 gcc aag atc gtg cag ctc ctg aag gagtgg acc gag gcc ttc ccc tat 240 Ala Lys Ile Val Gln Leu Leu Lys Glu TrpThr Glu Ala Phe Pro Tyr 65 70 75 gac ttc cag gat gag aag gcc atg gcc gagctg aaa gcc atc aca cac 288 Asp Phe Gln Asp Glu Lys Ala Met Ala Glu LeuLys Ala Ile Thr His 80 85 90 cgt gtc acc cag tgt gat gag gag aat ggc acagtg aag aag gcc att 336 Arg Val Thr Gln Cys Asp Glu Glu Asn Gly Thr ValLys Lys Ala Ile 95 100 105 110 gcc cag atg aca cag agc ctg ttg ctg tccttg gct gcc cgg agc cag 384 Ala Gln Met Thr Gln Ser Leu Leu Leu Ser LeuAla Ala Arg Ser Gln 115 120 125 ctc cag gaa ctg cga gag aag ctc cgg ccaccg gct gta gac aag ggg 432 Leu Gln Glu Leu Arg Glu Lys Leu Arg Pro ProAla Val Asp Lys Gly 130 135 140 ccc atc ctc aag acc aag cca cca gcc gcccag aag gac atc ctg ggc 480 Pro Ile Leu Lys Thr Lys Pro Pro Ala Ala GlnLys Asp Ile Leu Gly 145 150 155 gtg tgc tgc gac ccc ctg gtg ctg gcc cagcag ctg act cac att gag 528 Val Cys Cys Asp Pro Leu Val Leu Ala Gln GlnLeu Thr His Ile Glu 160 165 170 ctg gac agg gtc agc agc att tac cct gaggac ttg atg cag atc gtc 576 Leu Asp Arg Val Ser Ser Ile Tyr Pro Glu AspLeu Met Gln Ile Val 175 180 185 190 agc cac atg gac tcc ttg gac aac cacagg tgc cga ggg gac ctg acc 624 Ser His Met Asp Ser Leu Asp Asn His ArgCys Arg Gly Asp Leu Thr 195 200 205 aag acc tac agc ctg gag gcc tat gacaac tgg ttc aac tgc ctg agc 672 Lys Thr Tyr Ser Leu Glu Ala Tyr Asp AsnTrp Phe Asn Cys Leu Ser 210 215 220 atg ctg gtg gcc act gag gtg tgc cgggta gtg aag aag aaa cac cgg 720 Met Leu Val Ala Thr Glu Val Cys Arg ValVal Lys Lys Lys His Arg 225 230 235 acc cgc atg ttg gag ttc ttc att gatgtg gcc cgg gag tgc ttc aac 768 Thr Arg Met Leu Glu Phe Phe Ile Asp ValAla Arg Glu Cys Phe Asn 240 245 250 atc ggg aac ttc aac tcc atg atg gccatc atc gca gct ggc atg aac 816 Ile Gly Asn Phe Asn Ser Met Met Ala IleIle Ala Ala Gly Met Asn 255 260 265 270 ctc agt cct gtg gca agg ctg aagaaa act tgg tcc aag gtc aag aca 864 Leu Ser Pro Val Ala Arg Leu Lys LysThr Trp Ser Lys Val Lys Thr 275 280 285 gcc aag ttt gat gtc ttg gag catcac atg gac ccg tcc agc aac ttc 912 Ala Lys Phe Asp Val Leu Glu His HisMet Asp Pro Ser Ser Asn Phe 290 295 300 tgc aac tac cgt aca gcc ctg cagggg gcc acg cag agg tcc cag atg 960 Cys Asn Tyr Arg Thr Ala Leu Gln GlyAla Thr Gln Arg Ser Gln Met 305 310 315 gcc aac agc agc cgt gaa aag atcgtc atc cct gtg ttc aac ctc ttc 1008 Ala Asn Ser Ser Arg Glu Lys Ile ValIle Pro Val Phe Asn Leu Phe 320 325 330 gtt aag gac atc tac ttc ctg cacaaa atc cat acc aac cac ctg ccc 1056 Val Lys Asp Ile Tyr Phe Leu His LysIle His Thr Asn His Leu Pro 335 340 345 350 aac ggg cac att aac ttt aagcag aaa ttc tgg gag atc tcc aga cag 1104 Asn Gly His Ile Asn Phe Lys GlnLys Phe Trp Glu Ile Ser Arg Gln 355 360 365 atc cat gag ttc atg aca tggaca cag gta gag tgt cct ttc gag aag 1152 Ile His Glu Phe Met Thr Trp ThrGln Val Glu Cys Pro Phe Glu Lys 370 375 380 gac aag aag att cag agt tacctg ctc acg gcg ccc atc tac agc gag 1200 Asp Lys Lys Ile Gln Ser Tyr LeuLeu Thr Ala Pro Ile Tyr Ser Glu 385 390 395 gaa gct ctc ttc gtc gcc tccttt gaa agt gag ggt ccc gag aac cac 1248 Glu Ala Leu Phe Val Ala Ser PheGlu Ser Glu Gly Pro Glu Asn His 400 405 410 atg gaa aaa gac agc tgg aagacc ctc agg taggagggc 1287 Met Glu Lys Asp Ser Trp Lys Thr Leu Arg 415420 10 424 PRT Homo sapiens 10 Met Glu His Leu Val Pro Thr Val Asp TyrTyr Pro Asp Arg Thr Tyr 1 5 10 15 Ile Phe Thr Phe Leu Leu Ser Ser ArgVal Phe Met Pro Pro His Asp 20 25 30 Leu Leu Ala Arg Val Gly Gln Ile CysVal Glu Gln Lys Gln Gln Leu 35 40 45 Glu Ala Gly Pro Glu Lys Gln Ala LysLeu Lys Ser Phe Ser Ala Lys 50 55 60 Ile Val Gln Leu Leu Lys Glu Trp ThrGlu Ala Phe Pro Tyr Asp Phe 65 70 75 80 Gln Asp Glu Lys Ala Met Ala GluLeu Lys Ala Ile Thr His Arg Val 85 90 95 Thr Gln Cys Asp Glu Glu Asn GlyThr Val Lys Lys Ala Ile Ala Gln 100 105 110 Met Thr Gln Ser Leu Leu LeuSer Leu Ala Ala Arg Ser Gln Leu Gln 115 120 125 Glu Leu Arg Glu Lys LeuArg Pro Pro Ala Val Asp Lys Gly Pro Ile 130 135 140 Leu Lys Thr Lys ProPro Ala Ala Gln Lys Asp Ile Leu Gly Val Cys 145 150 155 160 Cys Asp ProLeu Val Leu Ala Gln Gln Leu Thr His Ile Glu Leu Asp 165 170 175 Arg ValSer Ser Ile Tyr Pro Glu Asp Leu Met Gln Ile Val Ser His 180 185 190 MetAsp Ser Leu Asp Asn His Arg Cys Arg Gly Asp Leu Thr Lys Thr 195 200 205Tyr Ser Leu Glu Ala Tyr Asp Asn Trp Phe Asn Cys Leu Ser Met Leu 210 215220 Val Ala Thr Glu Val Cys Arg Val Val Lys Lys Lys His Arg Thr Arg 225230 235 240 Met Leu Glu Phe Phe Ile Asp Val Ala Arg Glu Cys Phe Asn IleGly 245 250 255 Asn Phe Asn Ser Met Met Ala Ile Ile Ala Ala Gly Met AsnLeu Ser 260 265 270 Pro Val Ala Arg Leu Lys Lys Thr Trp Ser Lys Val LysThr Ala Lys 275 280 285 Phe Asp Val Leu Glu His His Met Asp Pro Ser SerAsn Phe Cys Asn 290 295 300 Tyr Arg Thr Ala Leu Gln Gly Ala Thr Gln ArgSer Gln Met Ala Asn 305 310 315 320 Ser Ser Arg Glu Lys Ile Val Ile ProVal Phe Asn Leu Phe Val Lys 325 330 335 Asp Ile Tyr Phe Leu His Lys IleHis Thr Asn His Leu Pro Asn Gly 340 345 350 His Ile Asn Phe Lys Gln LysPhe Trp Glu Ile Ser Arg Gln Ile His 355 360 365 Glu Phe Met Thr Trp ThrGln Val Glu Cys Pro Phe Glu Lys Asp Lys 370 375 380 Lys Ile Gln Ser TyrLeu Leu Thr Ala Pro Ile Tyr Ser Glu Glu Ala 385 390 395 400 Leu Phe ValAla Ser Phe Glu Ser Glu Gly Pro Glu Asn His Met Glu 405 410 415 Lys AspSer Trp Lys Thr Leu Arg 420 11 1269 DNA Homo sapiens CDS (4)..(1266) 11ctg atg gag cac ctt gtt ccc acg gtg gac tat tac ccc gat agg acg 48 MetGlu His Leu Val Pro Thr Val Asp Tyr Tyr Pro Asp Arg Thr 1 5 10 15 tacatc ttc acc ttt ctc ctg agc tcc cgg gtc ttt atg ccc cct cat 96 Tyr IlePhe Thr Phe Leu Leu Ser Ser Arg Val Phe Met Pro Pro His 20 25 30 gac ctgctg gcc cgc gtg ggg cag atc tgc gtg gag cag aag cag cag 144 Asp Leu LeuAla Arg Val Gly Gln Ile Cys Val Glu Gln Lys Gln Gln 35 40 45 ctg gaa gccggg cct gaa aag gcc aag ctg aag tct ttc tca gcc aag 192 Leu Glu Ala GlyPro Glu Lys Ala Lys Leu Lys Ser Phe Ser Ala Lys 50 55 60 atc gtg cag ctcctg aag gag tgg acc gag gcc ttc ccc tat gac ttc 240 Ile Val Gln Leu LeuLys Glu Trp Thr Glu Ala Phe Pro Tyr Asp Phe 65 70 75 cag gat gag aag gccatg gcc gag ctg aaa gcc atc aca cac cgt gtc 288 Gln Asp Glu Lys Ala MetAla Glu Leu Lys Ala Ile Thr His Arg Val 80 85 90 95 acc cag tgt gat gaggag aat ggc aca gtg agg aag gcc att gcc cag 336 Thr Gln Cys Asp Glu GluAsn Gly Thr Val Arg Lys Ala Ile Ala Gln 100 105 110 atg aca cag agc ctgttg ctg tcc ttg gct gcc cgg agc cag ctc cag 384 Met Thr Gln Ser Leu LeuLeu Ser Leu Ala Ala Arg Ser Gln Leu Gln 115 120 125 gaa ctg cga gag aagctc cgg cca ccg gct gta gac aag ggg ccc atc 432 Glu Leu Arg Glu Lys LeuArg Pro Pro Ala Val Asp Lys Gly Pro Ile 130 135 140 ctc aag acc aag ccacca gcc gcc cag aag gac atc ctg ggc gtg tgc 480 Leu Lys Thr Lys Pro ProAla Ala Gln Lys Asp Ile Leu Gly Val Cys 145 150 155 tgc gac ccc ctg gtgctg gcc cag cag ctg act cac att gag ctg gac 528 Cys Asp Pro Leu Val LeuAla Gln Gln Leu Thr His Ile Glu Leu Asp 160 165 170 175 agg gtc agc agcatt tac cct gag gac ttg atg cag atc gtc agc cac 576 Arg Val Ser Ser IleTyr Pro Glu Asp Leu Met Gln Ile Val Ser His 180 185 190 atg gac tcc ttggac aac cac agg tgc cga ggg gac ctg acc aag acc 624 Met Asp Ser Leu AspAsn His Arg Cys Arg Gly Asp Leu Thr Lys Thr 195 200 205 tac agc ctg gaggcc tat gac aac tgg ttc aac tgc ctg agc atg cag 672 Tyr Ser Leu Glu AlaTyr Asp Asn Trp Phe Asn Cys Leu Ser Met Gln 210 215 220 gtg gcc act gaggtg tgc cgg gtg gtg aag aag aaa cac cgg gcc cgc 720 Val Ala Thr Glu ValCys Arg Val Val Lys Lys Lys His Arg Ala Arg 225 230 235 atg ttg gag ttcttc att gat gtg gcc cgg gag tgc ttc aac atc ggg 768 Met Leu Glu Phe PheIle Asp Val Ala Arg Glu Cys Phe Asn Ile Gly 240 245 250 255 aac ttc aactcc atg atg gcc atc atc tct ggc atg aac ctc agt cct 816 Asn Phe Asn SerMet Met Ala Ile Ile Ser Gly Met Asn Leu Ser Pro 260 265 270 gtg gca aggctg aag aaa act tgg tcc aag gtc aag aca gcc aag ttt 864 Val Ala Arg LeuLys Lys Thr Trp Ser Lys Val Lys Thr Ala Lys Phe 275 280 285 gat gtc ttggag cat cac atg gac ccg tcc agc aac ttc tgc aac tac 912 Asp Val Leu GluHis His Met Asp Pro Ser Ser Asn Phe Cys Asn Tyr 290 295 300 cgt aca gccctg cag ggg gcc acg cag agg tcc cag atg gcc aac agc 960 Arg Thr Ala LeuGln Gly Ala Thr Gln Arg Ser Gln Met Ala Asn Ser 305 310 315 agc cgt gaaaag atc gtc atc cct gtg ttc aac ccc ttc gtt aag gac 1008 Ser Arg Glu LysIle Val Ile Pro Val Phe Asn Pro Phe Val Lys Asp 320 325 330 335 atc tacttc ctg cac aaa atc cat acc aac cac ctg ccc aac ggg cac 1056 Ile Tyr PheLeu His Lys Ile His Thr Asn His Leu Pro Asn Gly His 340 345 350 att aacttt aag aaa ttc tgg gag atc tcc aga cag atc cat gag ttc 1104 Ile Asn PheLys Lys Phe Trp Glu Ile Ser Arg Gln Ile His Glu Phe 355 360 365 atg acatgg aca cag gta gag tgt cct ttc gag aag gac aag aag att 1152 Met Thr TrpThr Gln Val Glu Cys Pro Phe Glu Lys Asp Lys Lys Ile 370 375 380 cag agttac ctg ctc acg gcg ccc atc tac agc gag gaa gct ctc ttc 1200 Gln Ser TyrLeu Leu Thr Ala Pro Ile Tyr Ser Glu Glu Ala Leu Phe 385 390 395 gtc gcctcc ttt gaa agt gag ggt ccc gag aac cac atg gaa aaa gac 1248 Val Ala SerPhe Glu Ser Glu Gly Pro Glu Asn His Met Glu Lys Asp 400 405 410 415 agctgg aag acc ctc agg tag 1269 Ser Trp Lys Thr Leu Arg 420 12 421 PRT Homosapiens 12 Met Glu His Leu Val Pro Thr Val Asp Tyr Tyr Pro Asp Arg ThrTyr 1 5 10 15 Ile Phe Thr Phe Leu Leu Ser Ser Arg Val Phe Met Pro ProHis Asp 20 25 30 Leu Leu Ala Arg Val Gly Gln Ile Cys Val Glu Gln Lys GlnGln Leu 35 40 45 Glu Ala Gly Pro Glu Lys Ala Lys Leu Lys Ser Phe Ser AlaLys Ile 50 55 60 Val Gln Leu Leu Lys Glu Trp Thr Glu Ala Phe Pro Tyr AspPhe Gln 65 70 75 80 Asp Glu Lys Ala Met Ala Glu Leu Lys Ala Ile Thr HisArg Val Thr 85 90 95 Gln Cys Asp Glu Glu Asn Gly Thr Val Arg Lys Ala IleAla Gln Met 100 105 110 Thr Gln Ser Leu Leu Leu Ser Leu Ala Ala Arg SerGln Leu Gln Glu 115 120 125 Leu Arg Glu Lys Leu Arg Pro Pro Ala Val AspLys Gly Pro Ile Leu 130 135 140 Lys Thr Lys Pro Pro Ala Ala Gln Lys AspIle Leu Gly Val Cys Cys 145 150 155 160 Asp Pro Leu Val Leu Ala Gln GlnLeu Thr His Ile Glu Leu Asp Arg 165 170 175 Val Ser Ser Ile Tyr Pro GluAsp Leu Met Gln Ile Val Ser His Met 180 185 190 Asp Ser Leu Asp Asn HisArg Cys Arg Gly Asp Leu Thr Lys Thr Tyr 195 200 205 Ser Leu Glu Ala TyrAsp Asn Trp Phe Asn Cys Leu Ser Met Gln Val 210 215 220 Ala Thr Glu ValCys Arg Val Val Lys Lys Lys His Arg Ala Arg Met 225 230 235 240 Leu GluPhe Phe Ile Asp Val Ala Arg Glu Cys Phe Asn Ile Gly Asn 245 250 255 PheAsn Ser Met Met Ala Ile Ile Ser Gly Met Asn Leu Ser Pro Val 260 265 270Ala Arg Leu Lys Lys Thr Trp Ser Lys Val Lys Thr Ala Lys Phe Asp 275 280285 Val Leu Glu His His Met Asp Pro Ser Ser Asn Phe Cys Asn Tyr Arg 290295 300 Thr Ala Leu Gln Gly Ala Thr Gln Arg Ser Gln Met Ala Asn Ser Ser305 310 315 320 Arg Glu Lys Ile Val Ile Pro Val Phe Asn Pro Phe Val LysAsp Ile 325 330 335 Tyr Phe Leu His Lys Ile His Thr Asn His Leu Pro AsnGly His Ile 340 345 350 Asn Phe Lys Lys Phe Trp Glu Ile Ser Arg Gln IleHis Glu Phe Met 355 360 365 Thr Trp Thr Gln Val Glu Cys Pro Phe Glu LysAsp Lys Lys Ile Gln 370 375 380 Ser Tyr Leu Leu Thr Ala Pro Ile Tyr SerGlu Glu Ala Leu Phe Val 385 390 395 400 Ala Ser Phe Glu Ser Glu Gly ProGlu Asn His Met Glu Lys Asp Ser 405 410 415 Trp Lys Thr Leu Arg 420 131259 DNA Homo sapiens CDS (6)..(1253) 13 tggcc atg gcg tcc ccg gcc atcggg cag cgc ccg tac ccg cta cta ttg 50 Met Ala Ser Pro Ala Ile Gly GlnArg Pro Tyr Pro Leu Leu Leu 1 5 10 15 gac ccc gag ccg ccg cgc tat ctacag agc ctg agc ggc ccc gag cta 98 Asp Pro Glu Pro Pro Arg Tyr Leu GlnSer Leu Ser Gly Pro Glu Leu 20 25 30 ccg ccg ccg ccc ccc gac cgg tcc tcgcgc ctc tgt gtc ccg gcg ccc 146 Pro Pro Pro Pro Pro Asp Arg Ser Ser ArgLeu Cys Val Pro Ala Pro 35 40 45 ctc tcc act gcg ccc ggg gcg cgc gag gggcgc agc gcc cgg agg gct 194 Leu Ser Thr Ala Pro Gly Ala Arg Glu Gly ArgSer Ala Arg Arg Ala 50 55 60 gcc cgg ggg aac ctg gag ccc ccg ccc cgg gcctcc cga ccc gct cgc 242 Ala Arg Gly Asn Leu Glu Pro Pro Pro Arg Ala SerArg Pro Ala Arg 65 70 75 ccg ctc cgg cct ggt ctg cag cag aga ctg cgg cggcgg cct gga gcg 290 Pro Leu Arg Pro Gly Leu Gln Gln Arg Leu Arg Arg ArgPro Gly Ala 80 85 90 95 ccc cga ccc cgc gac gtg cgg agc atc ttc gag cagccg cag gat ccc 338 Pro Arg Pro Arg Asp Val Arg Ser Ile Phe Glu Gln ProGln Asp Pro 100 105 110 aga gtc ccg gcg gag cga ggc gag ggg cac tgc ttcgcc gag ttg gtg 386 Arg Val Pro Ala Glu Arg Gly Glu Gly His Cys Phe AlaGlu Leu Val 115 120 125 ctg ccg ggc ggc ccc ggc tgg tgt gac ctg tgc ggacga gag gtg ctg 434 Leu Pro Gly Gly Pro Gly Trp Cys Asp Leu Cys Gly ArgGlu Val Leu 130 135 140 cgg cag gcg ctg cgc tgc act gac tgt aaa ttc acctgt cac cca gaa 482 Arg Gln Ala Leu Arg Cys Thr Asp Cys Lys Phe Thr CysHis Pro Glu 145 150 155 tgc cgc agc ctg atc cag ttg gac tgc agt cag caggag ggt tta tcc 530 Cys Arg Ser Leu Ile Gln Leu Asp Cys Ser Gln Gln GluGly Leu Ser 160 165 170 175 cgg gac aga ccc tct cca gaa agc acc ctc accgtg acc ttc agc cag 578 Arg Asp Arg Pro Ser Pro Glu Ser Thr Leu Thr ValThr Phe Ser Gln 180 185 190 aat gtc tgt aaa cct gtg gag gag aca cag cgcccg ccc aca ctg cag 626 Asn Val Cys Lys Pro Val Glu Glu Thr Gln Arg ProPro Thr Leu Gln 195 200 205 gag atc aag cag aag atc gac agc tac aac acgcga gag aag aac tgc 674 Glu Ile Lys Gln Lys Ile Asp Ser Tyr Asn Thr ArgGlu Lys Asn Cys 210 215 220 ctg ggc atg aaa ctg agt gaa gac ggc acc tacacg ggt ttc atc aaa 722 Leu Gly Met Lys Leu Ser Glu Asp Gly Thr Tyr ThrGly Phe Ile Lys 225 230 235 gtg cat ctg aaa ctc cgg cgg cct gtg acg gtgcct gct ggg atc cgg 770 Val His Leu Lys Leu Arg Arg Pro Val Thr Val ProAla Gly Ile Arg 240 245 250 255 ccc cag tcc atc tat gat gcc atc aag gaggtg aac ctg gcg gct acc 818 Pro Gln Ser Ile Tyr Asp Ala Ile Lys Glu ValAsn Leu Ala Ala Thr 260 265 270 acg gac aag cgg aca tcc ttc tac ctg ccccta gat gcc atc aag cag 866 Thr Asp Lys Arg Thr Ser Phe Tyr Leu Pro LeuAsp Ala Ile Lys Gln 275 280 285 ctg cac atc agc agc acc acc acc gtc agtgag gtc atc cag ggg ctg 914 Leu His Ile Ser Ser Thr Thr Thr Val Ser GluVal Ile Gln Gly Leu 290 295 300 ctc aag aag ttc atg gtt gtg gac aat ccccag aag ttt gca ctt ttt 962 Leu Lys Lys Phe Met Val Val Asp Asn Pro GlnLys Phe Ala Leu Phe 305 310 315 aag cgg ata cac aag gac gga caa gtg ctcttc cag aaa ctc tcc att 1010 Lys Arg Ile His Lys Asp Gly Gln Val Leu PheGln Lys Leu Ser Ile 320 325 330 335 gct gac cgc ccc ctc tac ctg cgc ctgctt gct ggg cct gac acg gag 1058 Ala Asp Arg Pro Leu Tyr Leu Arg Leu LeuAla Gly Pro Asp Thr Glu 340 345 350 gtc ctc agc ttt gtg cta aag gag aatgaa act gga gag gta gag tgg 1106 Val Leu Ser Phe Val Leu Lys Glu Asn GluThr Gly Glu Val Glu Trp 355 360 365 gat gcc ttc tcc atc cct gaa ctt cagaac ttc cta aca atc ctg gaa 1154 Asp Ala Phe Ser Ile Pro Glu Leu Gln AsnPhe Leu Thr Ile Leu Glu 370 375 380 aaa gag gag cag gac aaa atc caa caagtg caa aag aag tat gac aag 1202 Lys Glu Glu Gln Asp Lys Ile Gln Gln ValGln Lys Lys Tyr Asp Lys 385 390 395 ttt agg cag aaa ctg gag gag gcc ttaaga gaa tcc cag ggc aaa cct 1250 Phe Arg Gln Lys Leu Glu Glu Ala Leu ArgGlu Ser Gln Gly Lys Pro 400 405 410 415 ggg taaccg 1259 Gly 14 416 PRTHomo sapiens 14 Met Ala Ser Pro Ala Ile Gly Gln Arg Pro Tyr Pro Leu LeuLeu Asp 1 5 10 15 Pro Glu Pro Pro Arg Tyr Leu Gln Ser Leu Ser Gly ProGlu Leu Pro 20 25 30 Pro Pro Pro Pro Asp Arg Ser Ser Arg Leu Cys Val ProAla Pro Leu 35 40 45 Ser Thr Ala Pro Gly Ala Arg Glu Gly Arg Ser Ala ArgArg Ala Ala 50 55 60 Arg Gly Asn Leu Glu Pro Pro Pro Arg Ala Ser Arg ProAla Arg Pro 65 70 75 80 Leu Arg Pro Gly Leu Gln Gln Arg Leu Arg Arg ArgPro Gly Ala Pro 85 90 95 Arg Pro Arg Asp Val Arg Ser Ile Phe Glu Gln ProGln Asp Pro Arg 100 105 110 Val Pro Ala Glu Arg Gly Glu Gly His Cys PheAla Glu Leu Val Leu 115 120 125 Pro Gly Gly Pro Gly Trp Cys Asp Leu CysGly Arg Glu Val Leu Arg 130 135 140 Gln Ala Leu Arg Cys Thr Asp Cys LysPhe Thr Cys His Pro Glu Cys 145 150 155 160 Arg Ser Leu Ile Gln Leu AspCys Ser Gln Gln Glu Gly Leu Ser Arg 165 170 175 Asp Arg Pro Ser Pro GluSer Thr Leu Thr Val Thr Phe Ser Gln Asn 180 185 190 Val Cys Lys Pro ValGlu Glu Thr Gln Arg Pro Pro Thr Leu Gln Glu 195 200 205 Ile Lys Gln LysIle Asp Ser Tyr Asn Thr Arg Glu Lys Asn Cys Leu 210 215 220 Gly Met LysLeu Ser Glu Asp Gly Thr Tyr Thr Gly Phe Ile Lys Val 225 230 235 240 HisLeu Lys Leu Arg Arg Pro Val Thr Val Pro Ala Gly Ile Arg Pro 245 250 255Gln Ser Ile Tyr Asp Ala Ile Lys Glu Val Asn Leu Ala Ala Thr Thr 260 265270 Asp Lys Arg Thr Ser Phe Tyr Leu Pro Leu Asp Ala Ile Lys Gln Leu 275280 285 His Ile Ser Ser Thr Thr Thr Val Ser Glu Val Ile Gln Gly Leu Leu290 295 300 Lys Lys Phe Met Val Val Asp Asn Pro Gln Lys Phe Ala Leu PheLys 305 310 315 320 Arg Ile His Lys Asp Gly Gln Val Leu Phe Gln Lys LeuSer Ile Ala 325 330 335 Asp Arg Pro Leu Tyr Leu Arg Leu Leu Ala Gly ProAsp Thr Glu Val 340 345 350 Leu Ser Phe Val Leu Lys Glu Asn Glu Thr GlyGlu Val Glu Trp Asp 355 360 365 Ala Phe Ser Ile Pro Glu Leu Gln Asn PheLeu Thr Ile Leu Glu Lys 370 375 380 Glu Glu Gln Asp Lys Ile Gln Gln ValGln Lys Lys Tyr Asp Lys Phe 385 390 395 400 Arg Gln Lys Leu Glu Glu AlaLeu Arg Glu Ser Gln Gly Lys Pro Gly 405 410 415 15 1293 DNA Homo sapiensCDS (15)..(1286) 15 cttgcctgcc tgcc atg gcc gac aag gaa gca gcc ttt gacgac gca gtg 50 Met Ala Asp Lys Glu Ala Ala Phe Asp Asp Ala Val 1 5 10gaa gaa cga gtg atc aac gag gag tac aaa aaa tgg aaa aag aac acc 98 GluGlu Arg Val Ile Asn Glu Glu Tyr Lys Lys Trp Lys Lys Asn Thr 15 20 25 cctttt ctt tat gat ttg gtg ttg acc cat gct ctg gag tgg ccc agc 146 Pro PheLeu Tyr Asp Leu Val Leu Thr His Ala Leu Glu Trp Pro Ser 30 35 40 cta actgcc cag tgg ctt cca gat gta acc aga cca gaa ggg aaa gat 194 Leu Thr AlaGln Trp Leu Pro Asp Val Thr Arg Pro Glu Gly Lys Asp 45 50 55 60 ttc agcatt cat caa ctt gtc ctg ggg aca tgc aca ttg gat gaa caa 242 Phe Ser IleHis Gln Leu Val Leu Gly Thr Cys Thr Leu Asp Glu Gln 65 70 75 aac cat ctcgtt ata gcc agt gtg caa ctc cct aat gat gac act cag 290 Asn His Leu ValIle Ala Ser Val Gln Leu Pro Asn Asp Asp Thr Gln 80 85 90 ttt gat gcg tcacac tac aac act gag aaa gga gaa ttt gga ggt ttt 338 Phe Asp Ala Ser HisTyr Asn Thr Glu Lys Gly Glu Phe Gly Gly Phe 95 100 105 tat tca gtt agagga aaa att gaa ata gaa atc aac atc aac cat gaa 386 Tyr Ser Val Arg GlyLys Ile Glu Ile Glu Ile Asn Ile Asn His Glu 110 115 120 gga gaa gtg aacaag gtc cgt tat atg ccc cag aac cct tgt atc atc 434 Gly Glu Val Asn LysVal Arg Tyr Met Pro Gln Asn Pro Cys Ile Ile 125 130 135 140 tca act aagact cct tcc agt gat gtt ctt gtc ttt gac tat aca aaa 482 Ser Thr Lys ThrPro Ser Ser Asp Val Leu Val Phe Asp Tyr Thr Lys 145 150 155 cac cct tctaaa cca gat cct tct gga gag tgc aat cca gac ttg tgt 530 His Pro Ser LysPro Asp Pro Ser Gly Glu Cys Asn Pro Asp Leu Cys 160 165 170 ctc tgt ggacat cag aag gaa ggc tat ggg ctt tct tgg aac cca aat 578 Leu Cys Gly HisGln Lys Glu Gly Tyr Gly Leu Ser Trp Asn Pro Asn 175 180 185 ctc tgt gggcac tta ctt ggt gct tca gat gac cac acc agc tgc ctg 626 Leu Cys Gly HisLeu Leu Gly Ala Ser Asp Asp His Thr Ser Cys Leu 190 195 200 tgg gac agcagt gct gtc cca aag gag gga aaa gtg gtg gat gtg aag 674 Trp Asp Ser SerAla Val Pro Lys Glu Gly Lys Val Val Asp Val Lys 205 210 215 220 atc atcttt aca ggg cat aca gca gta gta gaa gat gtt tcc tgg cat 722 Ile Ile PheThr Gly His Thr Ala Val Val Glu Asp Val Ser Trp His 225 230 235 ctg ctccat gag tct ctg ttt ggg tca gtt gct gat gat cag aaa ctt 770 Leu Leu HisGlu Ser Leu Phe Gly Ser Val Ala Asp Asp Gln Lys Leu 240 245 250 atg atttgg gat act tgt tca aac agt gct tcc aaa cca agc cat tca 818 Met Ile TrpAsp Thr Cys Ser Asn Ser Ala Ser Lys Pro Ser His Ser 255 260 265 gtt gacgct cac act gct gaa gtg tgc ctc tct ttc aat cct tat agt 866 Val Asp AlaHis Thr Ala Glu Val Cys Leu Ser Phe Asn Pro Tyr Ser 270 275 280 gag ttcatt ctt gcc aca gga tcc gct gac aag act gtt gcc ttg cgg 914 Glu Phe IleLeu Ala Thr Gly Ser Ala Asp Lys Thr Val Ala Leu Arg 285 290 295 300 gatctg aga aat ctg aaa ctt aag ttg cat tcc ttt gaa tta ctt aag 962 Asp LeuArg Asn Leu Lys Leu Lys Leu His Ser Phe Glu Leu Leu Lys 305 310 315 gataaa ata ttc cag gtt cag tgg tca cct cac aat gag act att ttg 1010 Asp LysIle Phe Gln Val Gln Trp Ser Pro His Asn Glu Thr Ile Leu 320 325 330 gcttcc agt ggt acc aat cac aga ctg aat gtc tgg gat tta agt aaa 1058 Ala SerSer Gly Thr Asn His Arg Leu Asn Val Trp Asp Leu Ser Lys 335 340 345 attgga gag aaa caa tcc cca gaa gat aaa aaa gac agg cca cca gag 1106 Ile GlyGlu Lys Gln Ser Pro Glu Asp Lys Lys Asp Arg Pro Pro Glu 350 355 360 ttattg ttt att cat ggt ggt cac act gcc aag ata cct gat ttc tcc 1154 Leu LeuPhe Ile His Gly Gly His Thr Ala Lys Ile Pro Asp Phe Ser 365 370 375 380ggg aat ccc aac gaa cct tgg gtg att tgt tct gta cca gaa gac aat 1202 GlyAsn Pro Asn Glu Pro Trp Val Ile Cys Ser Val Pro Glu Asp Asn 385 390 395att atg caa gtg tgg caa atg gca gag aac att tac aac aat gaa gac 1250 IleMet Gln Val Trp Gln Met Ala Glu Asn Ile Tyr Asn Asn Glu Asp 400 405 410cct gaa gga agc gtg gat cca gaa gga caa gag tcc tagatat 1293 Pro Glu GlySer Val Asp Pro Glu Gly Gln Glu Ser 415 420 16 424 PRT Homo sapiens 16Met Ala Asp Lys Glu Ala Ala Phe Asp Asp Ala Val Glu Glu Arg Val 1 5 1015 Ile Asn Glu Glu Tyr Lys Lys Trp Lys Lys Asn Thr Pro Phe Leu Tyr 20 2530 Asp Leu Val Leu Thr His Ala Leu Glu Trp Pro Ser Leu Thr Ala Gln 35 4045 Trp Leu Pro Asp Val Thr Arg Pro Glu Gly Lys Asp Phe Ser Ile His 50 5560 Gln Leu Val Leu Gly Thr Cys Thr Leu Asp Glu Gln Asn His Leu Val 65 7075 80 Ile Ala Ser Val Gln Leu Pro Asn Asp Asp Thr Gln Phe Asp Ala Ser 8590 95 His Tyr Asn Thr Glu Lys Gly Glu Phe Gly Gly Phe Tyr Ser Val Arg100 105 110 Gly Lys Ile Glu Ile Glu Ile Asn Ile Asn His Glu Gly Glu ValAsn 115 120 125 Lys Val Arg Tyr Met Pro Gln Asn Pro Cys Ile Ile Ser ThrLys Thr 130 135 140 Pro Ser Ser Asp Val Leu Val Phe Asp Tyr Thr Lys HisPro Ser Lys 145 150 155 160 Pro Asp Pro Ser Gly Glu Cys Asn Pro Asp LeuCys Leu Cys Gly His 165 170 175 Gln Lys Glu Gly Tyr Gly Leu Ser Trp AsnPro Asn Leu Cys Gly His 180 185 190 Leu Leu Gly Ala Ser Asp Asp His ThrSer Cys Leu Trp Asp Ser Ser 195 200 205 Ala Val Pro Lys Glu Gly Lys ValVal Asp Val Lys Ile Ile Phe Thr 210 215 220 Gly His Thr Ala Val Val GluAsp Val Ser Trp His Leu Leu His Glu 225 230 235 240 Ser Leu Phe Gly SerVal Ala Asp Asp Gln Lys Leu Met Ile Trp Asp 245 250 255 Thr Cys Ser AsnSer Ala Ser Lys Pro Ser His Ser Val Asp Ala His 260 265 270 Thr Ala GluVal Cys Leu Ser Phe Asn Pro Tyr Ser Glu Phe Ile Leu 275 280 285 Ala ThrGly Ser Ala Asp Lys Thr Val Ala Leu Arg Asp Leu Arg Asn 290 295 300 LeuLys Leu Lys Leu His Ser Phe Glu Leu Leu Lys Asp Lys Ile Phe 305 310 315320 Gln Val Gln Trp Ser Pro His Asn Glu Thr Ile Leu Ala Ser Ser Gly 325330 335 Thr Asn His Arg Leu Asn Val Trp Asp Leu Ser Lys Ile Gly Glu Lys340 345 350 Gln Ser Pro Glu Asp Lys Lys Asp Arg Pro Pro Glu Leu Leu PheIle 355 360 365 His Gly Gly His Thr Ala Lys Ile Pro Asp Phe Ser Gly AsnPro Asn 370 375 380 Glu Pro Trp Val Ile Cys Ser Val Pro Glu Asp Asn IleMet Gln Val 385 390 395 400 Trp Gln Met Ala Glu Asn Ile Tyr Asn Asn GluAsp Pro Glu Gly Ser 405 410 415 Val Asp Pro Glu Gly Gln Glu Ser 420 171269 DNA Homo sapiens CDS (1)..(894) 17 atg gaa gga gac ttc tcg gtg tgcagg aac tgt aaa aga cat gta gtc 48 Met Glu Gly Asp Phe Ser Val Cys ArgAsn Cys Lys Arg His Val Val 1 5 10 15 tct gcc aac ttc acc ctc cat gaggct tac tgc ctg cgg ttc ctg gtc 96 Ser Ala Asn Phe Thr Leu His Glu AlaTyr Cys Leu Arg Phe Leu Val 20 25 30 ctg tgt ccg gag tgt gag gag cct gtcccc aag gaa acc atg gag gag 144 Leu Cys Pro Glu Cys Glu Glu Pro Val ProLys Glu Thr Met Glu Glu 35 40 45 cac tgc aag ctt gag cac cag cag gcc aatgag tgc cag gag cgc cct 192 His Cys Lys Leu Glu His Gln Gln Ala Asn GluCys Gln Glu Arg Pro 50 55 60 gtt gag tgt aag ttc tgc aaa ctg gac atg cagctc agc aag ctg gag 240 Val Glu Cys Lys Phe Cys Lys Leu Asp Met Gln LeuSer Lys Leu Glu 65 70 75 80 ctc cac gag tcc tac tgt ggc agc cgg aca gagctc tgc caa ggc tgt 288 Leu His Glu Ser Tyr Cys Gly Ser Arg Thr Glu LeuCys Gln Gly Cys 85 90 95 ggc cag ttc atc atg cac cgc atg ctc gcc cag cacaga gat gtc tgt 336 Gly Gln Phe Ile Met His Arg Met Leu Ala Gln His ArgAsp Val Cys 100 105 110 cgc agt gaa cag gcc cag ctc ggg aaa ggg gaa agaatt tca gct cct 384 Arg Ser Glu Gln Ala Gln Leu Gly Lys Gly Glu Arg IleSer Ala Pro 115 120 125 gaa agg gaa atc tac tgt cat tat tgc aac caa atgatt cca gaa aat 432 Glu Arg Glu Ile Tyr Cys His Tyr Cys Asn Gln Met IlePro Glu Asn 130 135 140 aag tat ttc cac cat atg ggt aaa tgt tgt cca gactca gag ttt aag 480 Lys Tyr Phe His His Met Gly Lys Cys Cys Pro Asp SerGlu Phe Lys 145 150 155 160 aaa cac ttt cct gtt gga aat cca gaa att cttcct tca tct ctt cca 528 Lys His Phe Pro Val Gly Asn Pro Glu Ile Leu ProSer Ser Leu Pro 165 170 175 agt caa gct gct gaa aat caa act tcc acg atggag aaa gat gtt cgt 576 Ser Gln Ala Ala Glu Asn Gln Thr Ser Thr Met GluLys Asp Val Arg 180 185 190 cca aag aca aga agt ata aac aga ttt cct cttcat tct gaa agt tca 624 Pro Lys Thr Arg Ser Ile Asn Arg Phe Pro Leu HisSer Glu Ser Ser 195 200 205 tca aag aaa gca cca aga agc aaa aac aaa accttg gat cca ctt ttg 672 Ser Lys Lys Ala Pro Arg Ser Lys Asn Lys Thr LeuAsp Pro Leu Leu 210 215 220 atg tca gag ccc aag ccc agg acc agc tcc cctaga gga gat aaa gca 720 Met Ser Glu Pro Lys Pro Arg Thr Ser Ser Pro ArgGly Asp Lys Ala 225 230 235 240 gcc tat gac att ctg agg aga tgt tct cagtgt ggc atc ctg ctt ccc 768 Ala Tyr Asp Ile Leu Arg Arg Cys Ser Gln CysGly Ile Leu Leu Pro 245 250 255 ctg ccg atc cta aat caa cat cag gag aaatgc cgg tgg tta gct tca 816 Leu Pro Ile Leu Asn Gln His Gln Glu Lys CysArg Trp Leu Ala Ser 260 265 270 tca aaa agg aaa aca agt gag aaa ttt cagcta gat ttg gaa aag gaa 864 Ser Lys Arg Lys Thr Ser Glu Lys Phe Gln LeuAsp Leu Glu Lys Glu 275 280 285 agg tac tac aaa ttc aaa aga ttt cac ttttaacactggc attcctgcct 914 Arg Tyr Tyr Lys Phe Lys Arg Phe His Phe 290295 acttgctgtg gtggtcttgt gaaaggtgat gggttttatt cgttgggctt taaaagaaaa974 ggtttggcag aactaaaaac aaaactcacg tatcatctca atagatacag aaaaggcttt1034 tgataaaatt caacttgact tcatgttaaa aaccctcaac aaaccaggcg tcgaaggaac1094 atacctcaaa ataataagag ccatctatga caaaaccaca gccaacatca tactgaatga1154 gcaaaagctg gagcattact cttgagaagt agaacaaggc acttcagtcc tattcaacat1214 agtactggaa gtctcgccac agcaatcagg caagagaaag aagtaaaagg caccc 126918 298 PRT Homo sapiens 18 Met Glu Gly Asp Phe Ser Val Cys Arg Asn CysLys Arg His Val Val 1 5 10 15 Ser Ala Asn Phe Thr Leu His Glu Ala TyrCys Leu Arg Phe Leu Val 20 25 30 Leu Cys Pro Glu Cys Glu Glu Pro Val ProLys Glu Thr Met Glu Glu 35 40 45 His Cys Lys Leu Glu His Gln Gln Ala AsnGlu Cys Gln Glu Arg Pro 50 55 60 Val Glu Cys Lys Phe Cys Lys Leu Asp MetGln Leu Ser Lys Leu Glu 65 70 75 80 Leu His Glu Ser Tyr Cys Gly Ser ArgThr Glu Leu Cys Gln Gly Cys 85 90 95 Gly Gln Phe Ile Met His Arg Met LeuAla Gln His Arg Asp Val Cys 100 105 110 Arg Ser Glu Gln Ala Gln Leu GlyLys Gly Glu Arg Ile Ser Ala Pro 115 120 125 Glu Arg Glu Ile Tyr Cys HisTyr Cys Asn Gln Met Ile Pro Glu Asn 130 135 140 Lys Tyr Phe His His MetGly Lys Cys Cys Pro Asp Ser Glu Phe Lys 145 150 155 160 Lys His Phe ProVal Gly Asn Pro Glu Ile Leu Pro Ser Ser Leu Pro 165 170 175 Ser Gln AlaAla Glu Asn Gln Thr Ser Thr Met Glu Lys Asp Val Arg 180 185 190 Pro LysThr Arg Ser Ile Asn Arg Phe Pro Leu His Ser Glu Ser Ser 195 200 205 SerLys Lys Ala Pro Arg Ser Lys Asn Lys Thr Leu Asp Pro Leu Leu 210 215 220Met Ser Glu Pro Lys Pro Arg Thr Ser Ser Pro Arg Gly Asp Lys Ala 225 230235 240 Ala Tyr Asp Ile Leu Arg Arg Cys Ser Gln Cys Gly Ile Leu Leu Pro245 250 255 Leu Pro Ile Leu Asn Gln His Gln Glu Lys Cys Arg Trp Leu AlaSer 260 265 270 Ser Lys Arg Lys Thr Ser Glu Lys Phe Gln Leu Asp Leu GluLys Glu 275 280 285 Arg Tyr Tyr Lys Phe Lys Arg Phe His Phe 290 295 19977 DNA Homo sapiens CDS (10)..(912) 19 atcgccctt atg gaa gga gac ttctcg gtg tgc agg aac tgt aaa aga cat 51 Met Glu Gly Asp Phe Ser Val CysArg Asn Cys Lys Arg His 1 5 10 gta gtc tct gcc aac ttc acc ctc cat gaggct tac tgc ctg cgg ttc 99 Val Val Ser Ala Asn Phe Thr Leu His Glu AlaTyr Cys Leu Arg Phe 15 20 25 30 ctg gtc ctg tgt ccg gag tgt gag gag cccgtc ccc aag gaa acc atg 147 Leu Val Leu Cys Pro Glu Cys Glu Glu Pro ValPro Lys Glu Thr Met 35 40 45 gag gag cac tgc aag ctt gag cac cag cag gttggg tgt acg atg tgt 195 Glu Glu His Cys Lys Leu Glu His Gln Gln Val GlyCys Thr Met Cys 50 55 60 cag cag agc atg cag aag tcc tcg ctg gag ttt cataag gcc aat gag 243 Gln Gln Ser Met Gln Lys Ser Ser Leu Glu Phe His LysAla Asn Glu 65 70 75 tgc cag gag cgc cct gtt gag tgt aag ttc tgc aaa ctggac atg cag 291 Cys Gln Glu Arg Pro Val Glu Cys Lys Phe Cys Lys Leu AspMet Gln 80 85 90 ctc agc aag ctg gag ctc cac gag tcc tac tgt ggc agc cggaca gag 339 Leu Ser Lys Leu Glu Leu His Glu Ser Tyr Cys Gly Ser Arg ThrGlu 95 100 105 110 ctc tgc caa ggc tgt ggc cag ttc atc atg cac cgc atgctc gcc cag 387 Leu Cys Gln Gly Cys Gly Gln Phe Ile Met His Arg Met LeuAla Gln 115 120 125 cac aga gat gtc tgt cgc agt gaa cag gcc cag ctc gggaag ggg gaa 435 His Arg Asp Val Cys Arg Ser Glu Gln Ala Gln Leu Gly LysGly Glu 130 135 140 aga att tca gct cct gaa agg gaa atc tac tgt cat tattgc aac caa 483 Arg Ile Ser Ala Pro Glu Arg Glu Ile Tyr Cys His Tyr CysAsn Gln 145 150 155 atg att cca gaa aat aag tat ttc cac cat atg ggt aaatgt tgt cca 531 Met Ile Pro Glu Asn Lys Tyr Phe His His Met Gly Lys CysCys Pro 160 165 170 gac tca gag ttt aag aaa cac ttt cct gtt gga aat ccagaa att ctt 579 Asp Ser Glu Phe Lys Lys His Phe Pro Val Gly Asn Pro GluIle Leu 175 180 185 190 cct tca tct ctt cca agt caa gct gct gaa aat caaact tcc acg atg 627 Pro Ser Ser Leu Pro Ser Gln Ala Ala Glu Asn Gln ThrSer Thr Met 195 200 205 gag aaa gat gtt cgt cca aag aca aga agt ata aacaga ttt cct ctt 675 Glu Lys Asp Val Arg Pro Lys Thr Arg Ser Ile Asn ArgPhe Pro Leu 210 215 220 cat tct gaa agt tca tca aag aaa gca cca aga agcaaa aac aaa acc 723 His Ser Glu Ser Ser Ser Lys Lys Ala Pro Arg Ser LysAsn Lys Thr 225 230 235 ttg gat cca ctt ttg atg tca gag ccc aag ccc aggacc agc tcc cct 771 Leu Asp Pro Leu Leu Met Ser Glu Pro Lys Pro Arg ThrSer Ser Pro 240 245 250 aga gga gat aaa gca gcc tat gac att ctg agg agatgt tct cag tgt 819 Arg Gly Asp Lys Ala Ala Tyr Asp Ile Leu Arg Arg CysSer Gln Cys 255 260 265 270 ggc atc ctg ctt ccc ctg ccg atc cta aat caacat cag gag aaa tgc 867 Gly Ile Leu Leu Pro Leu Pro Ile Leu Asn Gln HisGln Glu Lys Cys 275 280 285 cgg tgg tta gct tca tca aaa gga aaa caa gtgaga aat ttc agc 912 Arg Trp Leu Ala Ser Ser Lys Gly Lys Gln Val Arg AsnPhe Ser 290 295 300 tagatttgga aaaggaaagg tactacaaat tcaaaagatttcacttttaa cactggcatt 972 cctgc 977 20 301 PRT Homo sapiens 20 Met GluGly Asp Phe Ser Val Cys Arg Asn Cys Lys Arg His Val Val 1 5 10 15 SerAla Asn Phe Thr Leu His Glu Ala Tyr Cys Leu Arg Phe Leu Val 20 25 30 LeuCys Pro Glu Cys Glu Glu Pro Val Pro Lys Glu Thr Met Glu Glu 35 40 45 HisCys Lys Leu Glu His Gln Gln Val Gly Cys Thr Met Cys Gln Gln 50 55 60 SerMet Gln Lys Ser Ser Leu Glu Phe His Lys Ala Asn Glu Cys Gln 65 70 75 80Glu Arg Pro Val Glu Cys Lys Phe Cys Lys Leu Asp Met Gln Leu Ser 85 90 95Lys Leu Glu Leu His Glu Ser Tyr Cys Gly Ser Arg Thr Glu Leu Cys 100 105110 Gln Gly Cys Gly Gln Phe Ile Met His Arg Met Leu Ala Gln His Arg 115120 125 Asp Val Cys Arg Ser Glu Gln Ala Gln Leu Gly Lys Gly Glu Arg Ile130 135 140 Ser Ala Pro Glu Arg Glu Ile Tyr Cys His Tyr Cys Asn Gln MetIle 145 150 155 160 Pro Glu Asn Lys Tyr Phe His His Met Gly Lys Cys CysPro Asp Ser 165 170 175 Glu Phe Lys Lys His Phe Pro Val Gly Asn Pro GluIle Leu Pro Ser 180 185 190 Ser Leu Pro Ser Gln Ala Ala Glu Asn Gln ThrSer Thr Met Glu Lys 195 200 205 Asp Val Arg Pro Lys Thr Arg Ser Ile AsnArg Phe Pro Leu His Ser 210 215 220 Glu Ser Ser Ser Lys Lys Ala Pro ArgSer Lys Asn Lys Thr Leu Asp 225 230 235 240 Pro Leu Leu Met Ser Glu ProLys Pro Arg Thr Ser Ser Pro Arg Gly 245 250 255 Asp Lys Ala Ala Tyr AspIle Leu Arg Arg Cys Ser Gln Cys Gly Ile 260 265 270 Leu Leu Pro Leu ProIle Leu Asn Gln His Gln Glu Lys Cys Arg Trp 275 280 285 Leu Ala Ser SerLys Gly Lys Gln Val Arg Asn Phe Ser 290 295 300 21 525 DNA Homo sapiensCDS (61)..(471) 21 cgcgtggcgc ctctatattt ccccgagagg tgcgaggcggctgggcgcac tcggagcgcg 60 atg ggc gac tgg aag gtc tac atc agt gca gtg ctgcgg gac cag cgc 108 Met Gly Asp Trp Lys Val Tyr Ile Ser Ala Val Leu ArgAsp Gln Arg 1 5 10 15 atc gac gac gtg gcc atc gtg ggc cat gcg gac aacagc tgc gtg tgg 156 Ile Asp Asp Val Ala Ile Val Gly His Ala Asp Asn SerCys Val Trp 20 25 30 gct tcg cgg ccc ggg ggc ctg ctg gcg gcc atc tcg ccgcag gag gtg 204 Ala Ser Arg Pro Gly Gly Leu Leu Ala Ala Ile Ser Pro GlnGlu Val 35 40 45 ggc gtg ctc acg ggg ccg gac agg cac acc ttc ctg cag gcgggc ctg 252 Gly Val Leu Thr Gly Pro Asp Arg His Thr Phe Leu Gln Ala GlyLeu 50 55 60 agc gtg ggg ggc cgc cgc tgc tgc gtc atc cgc gac cac ctg ctggcc 300 Ser Val Gly Gly Arg Arg Cys Cys Val Ile Arg Asp His Leu Leu Ala65 70 75 80 gag ggt gac ggc gtg ctg gac gca cgc acc aag ggg ctg gac gcgcgc 348 Glu Gly Asp Gly Val Leu Asp Ala Arg Thr Lys Gly Leu Asp Ala Arg85 90 95 gcc gtg tgc gtg ggc cgt gcg ccg cgc gcg ctc ctg gtg cta atg ggc396 Ala Val Cys Val Gly Arg Ala Pro Arg Ala Leu Leu Val Leu Met Gly 100105 110 cga cgc ggc gta cat ggg ggc atc ctc aac aag acg gtg cac gaa ctc444 Arg Arg Gly Val His Gly Gly Ile Leu Asn Lys Thr Val His Glu Leu 115120 125 ata cgc ggg ctg cgc atg cag ggc gcc tagccggcca gccaggccgc 491Ile Arg Gly Leu Arg Met Gln Gly Ala 130 135 ccactggtag cgcgggccaaataaactgtg acct 525 22 137 PRT Homo sapiens 22 Met Gly Asp Trp Lys ValTyr Ile Ser Ala Val Leu Arg Asp Gln Arg 1 5 10 15 Ile Asp Asp Val AlaIle Val Gly His Ala Asp Asn Ser Cys Val Trp 20 25 30 Ala Ser Arg Pro GlyGly Leu Leu Ala Ala Ile Ser Pro Gln Glu Val 35 40 45 Gly Val Leu Thr GlyPro Asp Arg His Thr Phe Leu Gln Ala Gly Leu 50 55 60 Ser Val Gly Gly ArgArg Cys Cys Val Ile Arg Asp His Leu Leu Ala 65 70 75 80 Glu Gly Asp GlyVal Leu Asp Ala Arg Thr Lys Gly Leu Asp Ala Arg 85 90 95 Ala Val Cys ValGly Arg Ala Pro Arg Ala Leu Leu Val Leu Met Gly 100 105 110 Arg Arg GlyVal His Gly Gly Ile Leu Asn Lys Thr Val His Glu Leu 115 120 125 Ile ArgGly Leu Arg Met Gln Gly Ala 130 135 23 465 DNA Homo sapiens CDS(1)..(411) 23 atg ggc gac tgg aag gtc tac atc agt gca gtg ctg cgg gaccag cgc 48 Met Gly Asp Trp Lys Val Tyr Ile Ser Ala Val Leu Arg Asp GlnArg 1 5 10 15 atc gac gac gtg gcc atc gtg ggc cat gcg gac aac agc tgcgtg tgg 96 Ile Asp Asp Val Ala Ile Val Gly His Ala Asp Asn Ser Cys ValTrp 20 25 30 gct tcg cgg ccc ggg ggc ctg ctg gcg gcc atc tcg ccg cag gaggtg 144 Ala Ser Arg Pro Gly Gly Leu Leu Ala Ala Ile Ser Pro Gln Glu Val35 40 45 ggc gtg ctc acg ggg ccg gac agg cac acc ttc ctg cag gcg ggc ctg192 Gly Val Leu Thr Gly Pro Asp Arg His Thr Phe Leu Gln Ala Gly Leu 5055 60 agc gtg ggg ggc cgc cgc tgc tgc gtc atc cgc gac cac ctg ctg gcc240 Ser Val Gly Gly Arg Arg Cys Cys Val Ile Arg Asp His Leu Leu Ala 6570 75 80 gaa ggt gac ggc gtg ctg gac gca cgc acc aag ggg ctg gac gcg cgc288 Glu Gly Asp Gly Val Leu Asp Ala Arg Thr Lys Gly Leu Asp Ala Arg 8590 95 gcc gtg tgc gtg ggc cgt gcg ccg cgc gcg ctc ctg gtg cta atg ggc336 Ala Val Cys Val Gly Arg Ala Pro Arg Ala Leu Leu Val Leu Met Gly 100105 110 cga cgc ggc gta cat ggg ggc atc ctc aac aag acg gtg cac gaa ctc384 Arg Arg Gly Val His Gly Gly Ile Leu Asn Lys Thr Val His Glu Leu 115120 125 ata cgc ggg ctg cgc atg cag ggc gcc tagccggcca gccaggccgc 431Ile Arg Gly Leu Arg Met Gln Gly Ala 130 135 ccactggtag cgcgggccaaataaactgtg acct 465 24 137 PRT Homo sapiens 24 Met Gly Asp Trp Lys ValTyr Ile Ser Ala Val Leu Arg Asp Gln Arg 1 5 10 15 Ile Asp Asp Val AlaIle Val Gly His Ala Asp Asn Ser Cys Val Trp 20 25 30 Ala Ser Arg Pro GlyGly Leu Leu Ala Ala Ile Ser Pro Gln Glu Val 35 40 45 Gly Val Leu Thr GlyPro Asp Arg His Thr Phe Leu Gln Ala Gly Leu 50 55 60 Ser Val Gly Gly ArgArg Cys Cys Val Ile Arg Asp His Leu Leu Ala 65 70 75 80 Glu Gly Asp GlyVal Leu Asp Ala Arg Thr Lys Gly Leu Asp Ala Arg 85 90 95 Ala Val Cys ValGly Arg Ala Pro Arg Ala Leu Leu Val Leu Met Gly 100 105 110 Arg Arg GlyVal His Gly Gly Ile Leu Asn Lys Thr Val His Glu Leu 115 120 125 Ile ArgGly Leu Arg Met Gln Gly Ala 130 135 25 649 DNA Homo sapiens CDS(8)..(646) 25 cctgggc atg tgg tat gag atc aag gcc cag gta cac aac atccac ctg 49 Met Trp Tyr Glu Ile Lys Ala Gln Val His Asn Ile His Leu 1 510 tgc aaa gac aaa cat ggc aag act ggg ctg cag ctg cag acc acc aac 97Cys Lys Asp Lys His Gly Lys Thr Gly Leu Gln Leu Gln Thr Thr Asn 15 20 2530 aag ggg ctc ttt gtg cag gtc cag gcc aac acc act gca tcc ctc atg 145Lys Gly Leu Phe Val Gln Val Gln Ala Asn Thr Thr Ala Ser Leu Met 35 40 45ctg ctg tgc ttt ggg gac caa atc cta cag att gat ggg cat gac tgt 193 LeuLeu Cys Phe Gly Asp Gln Ile Leu Gln Ile Asp Gly His Asp Cys 50 55 60 gccaag tgg aac atg gaa aaa gcc cat gtt ata aga tgg gag tct ggt 241 Ala LysTrp Asn Met Glu Lys Ala His Val Ile Arg Trp Glu Ser Gly 65 70 75 gac aagatt gtt atg gtc att cag gac agg ata gtc cag tgg att gtc 289 Asp Lys IleVal Met Val Ile Gln Asp Arg Ile Val Gln Trp Ile Val 80 85 90 acc atg cacaag gac agc aca agc cat ggt ggc ttc atc atc aag aag 337 Thr Met His LysAsp Ser Thr Ser His Gly Gly Phe Ile Ile Lys Lys 95 100 105 110 gga aaggtc ttc cct gtg gtc aaa ggg agc tct gga ctc ttc acc aac 385 Gly Lys ValPhe Pro Val Val Lys Gly Ser Ser Gly Leu Phe Thr Asn 115 120 125 cac catgtg tgc cag gtt caa gaa cgt tta aca agc act gtg cag agt 433 His His ValCys Gln Val Gln Glu Arg Leu Thr Ser Thr Val Gln Ser 130 135 140 gtc attggg ctg aaa gag atc tca gag att ctg gcc aca gcc agg aac 481 Val Ile GlyLeu Lys Glu Ile Ser Glu Ile Leu Ala Thr Ala Arg Asn 145 150 155 att gtcacc ctg atc atc atc ccc act gtg atc tat gag cac ata gtc 529 Ile Val ThrLeu Ile Ile Ile Pro Thr Val Ile Tyr Glu His Ile Val 160 165 170 aaa aagttt tcc ctg acc cat cgc cac cac ata tgg acc act tca tcc 577 Lys Lys PheSer Leu Thr His Arg His His Ile Trp Thr Thr Ser Ser 175 180 185 190 cagatg cct gaa gcc aca gga ggg cag ctt agg ccc tcc cac cct cct 625 Gln MetPro Glu Ala Thr Gly Gly Gln Leu Arg Pro Ser His Pro Pro 195 200 205 gcagga aag gcc agc cac tct tga 649 Ala Gly Lys Ala Ser His Ser 210 26 213PRT Homo sapiens 26 Met Trp Tyr Glu Ile Lys Ala Gln Val His Asn Ile HisLeu Cys Lys 1 5 10 15 Asp Lys His Gly Lys Thr Gly Leu Gln Leu Gln ThrThr Asn Lys Gly 20 25 30 Leu Phe Val Gln Val Gln Ala Asn Thr Thr Ala SerLeu Met Leu Leu 35 40 45 Cys Phe Gly Asp Gln Ile Leu Gln Ile Asp Gly HisAsp Cys Ala Lys 50 55 60 Trp Asn Met Glu Lys Ala His Val Ile Arg Trp GluSer Gly Asp Lys 65 70 75 80 Ile Val Met Val Ile Gln Asp Arg Ile Val GlnTrp Ile Val Thr Met 85 90 95 His Lys Asp Ser Thr Ser His Gly Gly Phe IleIle Lys Lys Gly Lys 100 105 110 Val Phe Pro Val Val Lys Gly Ser Ser GlyLeu Phe Thr Asn His His 115 120 125 Val Cys Gln Val Gln Glu Arg Leu ThrSer Thr Val Gln Ser Val Ile 130 135 140 Gly Leu Lys Glu Ile Ser Glu IleLeu Ala Thr Ala Arg Asn Ile Val 145 150 155 160 Thr Leu Ile Ile Ile ProThr Val Ile Tyr Glu His Ile Val Lys Lys 165 170 175 Phe Ser Leu Thr HisArg His His Ile Trp Thr Thr Ser Ser Gln Met 180 185 190 Pro Glu Ala ThrGly Gly Gln Leu Arg Pro Ser His Pro Pro Ala Gly 195 200 205 Lys Ala SerHis Ser 210 27 814 DNA Homo sapiens CDS (12)..(791) 27 ctgccatcgc t atgtct ctg caa aag acc cct ccg acc cga gtg ttc gtg 50 Met Ser Leu Gln LysThr Pro Pro Thr Arg Val Phe Val 1 5 10 gaa ctg gtt ccc tgg gct gac cggagc cgg gag aac aac ctg gcc tca 98 Glu Leu Val Pro Trp Ala Asp Arg SerArg Glu Asn Asn Leu Ala Ser 15 20 25 ggg aga gag acg cta ccg ggc tta cgccac ccc ctc tcc tca aca caa 146 Gly Arg Glu Thr Leu Pro Gly Leu Arg HisPro Leu Ser Ser Thr Gln 30 35 40 45 gcc caa act gct acc cgc gag gtg caagta agc ggc acc tca gaa gtg 194 Ala Gln Thr Ala Thr Arg Glu Val Gln ValSer Gly Thr Ser Glu Val 50 55 60 tct gcg ggc cct gac cgg gcg cag gtg gtggtg cga gtg agc agc acc 242 Ser Ala Gly Pro Asp Arg Ala Gln Val Val ValArg Val Ser Ser Thr 65 70 75 aag gag gcg gca gcc gag gcc aaa aag agc gtttgt cgc cgt cta gat 290 Lys Glu Ala Ala Ala Glu Ala Lys Lys Ser Val CysArg Arg Leu Asp 80 85 90 tac atc acg cag agc ctc cag cag cag ggc ttt caggca gaa aat ata 338 Tyr Ile Thr Gln Ser Leu Gln Gln Gln Gly Phe Gln AlaGlu Asn Ile 95 100 105 act gtg aca aag gat ttt agg aga gtg gaa aat gcttat cac atg gaa 386 Thr Val Thr Lys Asp Phe Arg Arg Val Glu Asn Ala TyrHis Met Glu 110 115 120 125 gca gag gta tgt att aca ttt act gaa ttt ggaaaa atg caa aat att 434 Ala Glu Val Cys Ile Thr Phe Thr Glu Phe Gly LysMet Gln Asn Ile 130 135 140 tgt aac ttt ctt gtt gaa aag cta gat agc tctgtt gtc atc agc cca 482 Cys Asn Phe Leu Val Glu Lys Leu Asp Ser Ser ValVal Ile Ser Pro 145 150 155 ccc cag ttc tat cat act cca ggt tct gtt gagaat ctt cgg cgg caa 530 Pro Gln Phe Tyr His Thr Pro Gly Ser Val Glu AsnLeu Arg Arg Gln 160 165 170 gcc tgt ctt gtt gct gtt gag aat gcg tgg cgcaaa gct caa gaa gtc 578 Ala Cys Leu Val Ala Val Glu Asn Ala Trp Arg LysAla Gln Glu Val 175 180 185 tgt aac ctt gtt ggc caa acc tta gga aaa ccttta cta atc aaa gaa 626 Cys Asn Leu Val Gly Gln Thr Leu Gly Lys Pro LeuLeu Ile Lys Glu 190 195 200 205 gaa gaa aca aaa gaa tgg gaa ggc caa atagat gat cac cag tca tcc 674 Glu Glu Thr Lys Glu Trp Glu Gly Gln Ile AspAsp His Gln Ser Ser 210 215 220 aga ctc tca agt tca tta act gta caa caaaaa atc aaa agt gca aca 722 Arg Leu Ser Ser Ser Leu Thr Val Gln Gln LysIle Lys Ser Ala Thr 225 230 235 ata cat gct gct tca aaa gta ttt ata actttt gag gta aag gga aaa 770 Ile His Ala Ala Ser Lys Val Phe Ile Thr PheGlu Val Lys Gly Lys 240 245 250 gag aag aga aaa aag cac ctt tgaaattccaaacaaattat att 814 Glu Lys Arg Lys Lys His Leu 255 260 28 260 PRT Homosapiens 28 Met Ser Leu Gln Lys Thr Pro Pro Thr Arg Val Phe Val Glu LeuVal 1 5 10 15 Pro Trp Ala Asp Arg Ser Arg Glu Asn Asn Leu Ala Ser GlyArg Glu 20 25 30 Thr Leu Pro Gly Leu Arg His Pro Leu Ser Ser Thr Gln AlaGln Thr 35 40 45 Ala Thr Arg Glu Val Gln Val Ser Gly Thr Ser Glu Val SerAla Gly 50 55 60 Pro Asp Arg Ala Gln Val Val Val Arg Val Ser Ser Thr LysGlu Ala 65 70 75 80 Ala Ala Glu Ala Lys Lys Ser Val Cys Arg Arg Leu AspTyr Ile Thr 85 90 95 Gln Ser Leu Gln Gln Gln Gly Phe Gln Ala Glu Asn IleThr Val Thr 100 105 110 Lys Asp Phe Arg Arg Val Glu Asn Ala Tyr His MetGlu Ala Glu Val 115 120 125 Cys Ile Thr Phe Thr Glu Phe Gly Lys Met GlnAsn Ile Cys Asn Phe 130 135 140 Leu Val Glu Lys Leu Asp Ser Ser Val ValIle Ser Pro Pro Gln Phe 145 150 155 160 Tyr His Thr Pro Gly Ser Val GluAsn Leu Arg Arg Gln Ala Cys Leu 165 170 175 Val Ala Val Glu Asn Ala TrpArg Lys Ala Gln Glu Val Cys Asn Leu 180 185 190 Val Gly Gln Thr Leu GlyLys Pro Leu Leu Ile Lys Glu Glu Glu Thr 195 200 205 Lys Glu Trp Glu GlyGln Ile Asp Asp His Gln Ser Ser Arg Leu Ser 210 215 220 Ser Ser Leu ThrVal Gln Gln Lys Ile Lys Ser Ala Thr Ile His Ala 225 230 235 240 Ala SerLys Val Phe Ile Thr Phe Glu Val Lys Gly Lys Glu Lys Arg 245 250 255 LysLys His Leu 260 29 807 DNA Homo sapiens CDS (5)..(784) 29 cctt atg tctctg caa aag acc cct ccg acc cga gtg ttc gtg gaa ctg 49 Met Ser Leu GlnLys Thr Pro Pro Thr Arg Val Phe Val Glu Leu 1 5 10 15 gtt ccc tgg gctgac cgg agc cgg gag aac aac ctg gcc tca ggg aga 97 Val Pro Trp Ala AspArg Ser Arg Glu Asn Asn Leu Ala Ser Gly Arg 20 25 30 gag acg cta ccg ggctta cgc cac ccc ctc tcc tca aca caa gcc caa 145 Glu Thr Leu Pro Gly LeuArg His Pro Leu Ser Ser Thr Gln Ala Gln 35 40 45 act gct acc cgc gag gtgcaa gta agc ggc acc tca gaa gtg tct gcg 193 Thr Ala Thr Arg Glu Val GlnVal Ser Gly Thr Ser Glu Val Ser Ala 50 55 60 ggc cct gac cgg gcg cag gtggtg gtg cga gtg agc agc acc aag gag 241 Gly Pro Asp Arg Ala Gln Val ValVal Arg Val Ser Ser Thr Lys Glu 65 70 75 gcg gca gcc gag gcc aaa aag agcgtt tgt cgc cgt cta gat tac atc 289 Ala Ala Ala Glu Ala Lys Lys Ser ValCys Arg Arg Leu Asp Tyr Ile 80 85 90 95 acg cag agc ctc cag cag cag ggcgtg cag gca gaa aat ata act gtg 337 Thr Gln Ser Leu Gln Gln Gln Gly ValGln Ala Glu Asn Ile Thr Val 100 105 110 aca aag gat ttt agg aga gtg gaaaat gct tat cac atg gaa gca gag 385 Thr Lys Asp Phe Arg Arg Val Glu AsnAla Tyr His Met Glu Ala Glu 115 120 125 gtc tgc att aca ttt act gaa tttgga aaa atg caa aat att tgt aac 433 Val Cys Ile Thr Phe Thr Glu Phe GlyLys Met Gln Asn Ile Cys Asn 130 135 140 ttt ctt gtt gaa aag cta gat agctct gtt gtc atc agc cca ccc cag 481 Phe Leu Val Glu Lys Leu Asp Ser SerVal Val Ile Ser Pro Pro Gln 145 150 155 ttc tat cat act cca ggt tct gttgag aat ctt cga cgg caa gcc tgt 529 Phe Tyr His Thr Pro Gly Ser Val GluAsn Leu Arg Arg Gln Ala Cys 160 165 170 175 ctt gtt gct gtt gag aat gcgtgg cgc aaa gct caa gaa gtc tgt aac 577 Leu Val Ala Val Glu Asn Ala TrpArg Lys Ala Gln Glu Val Cys Asn 180 185 190 ctt gtt ggc caa acc tta ggaaaa cct tta cta atc aaa gaa gaa gaa 625 Leu Val Gly Gln Thr Leu Gly LysPro Leu Leu Ile Lys Glu Glu Glu 195 200 205 aca aaa gaa tgg gaa ggc caaata gat gat cac cag tca tcc aga ctc 673 Thr Lys Glu Trp Glu Gly Gln IleAsp Asp His Gln Ser Ser Arg Leu 210 215 220 tca agt tca tta act gta caacaa aaa atc aaa agt gca aca ata cat 721 Ser Ser Ser Leu Thr Val Gln GlnLys Ile Lys Ser Ala Thr Ile His 225 230 235 gct gct tca aaa gta ttt ataact ttt gag gta aag gga aaa gag aag 769 Ala Ala Ser Lys Val Phe Ile ThrPhe Glu Val Lys Gly Lys Glu Lys 240 245 250 255 aga aaa aag cac ctttgaaattcca aacaaattat att 807 Arg Lys Lys His Leu 260 30 260 PRT Homosapiens 30 Met Ser Leu Gln Lys Thr Pro Pro Thr Arg Val Phe Val Glu LeuVal 1 5 10 15 Pro Trp Ala Asp Arg Ser Arg Glu Asn Asn Leu Ala Ser GlyArg Glu 20 25 30 Thr Leu Pro Gly Leu Arg His Pro Leu Ser Ser Thr Gln AlaGln Thr 35 40 45 Ala Thr Arg Glu Val Gln Val Ser Gly Thr Ser Glu Val SerAla Gly 50 55 60 Pro Asp Arg Ala Gln Val Val Val Arg Val Ser Ser Thr LysGlu Ala 65 70 75 80 Ala Ala Glu Ala Lys Lys Ser Val Cys Arg Arg Leu AspTyr Ile Thr 85 90 95 Gln Ser Leu Gln Gln Gln Gly Val Gln Ala Glu Asn IleThr Val Thr 100 105 110 Lys Asp Phe Arg Arg Val Glu Asn Ala Tyr His MetGlu Ala Glu Val 115 120 125 Cys Ile Thr Phe Thr Glu Phe Gly Lys Met GlnAsn Ile Cys Asn Phe 130 135 140 Leu Val Glu Lys Leu Asp Ser Ser Val ValIle Ser Pro Pro Gln Phe 145 150 155 160 Tyr His Thr Pro Gly Ser Val GluAsn Leu Arg Arg Gln Ala Cys Leu 165 170 175 Val Ala Val Glu Asn Ala TrpArg Lys Ala Gln Glu Val Cys Asn Leu 180 185 190 Val Gly Gln Thr Leu GlyLys Pro Leu Leu Ile Lys Glu Glu Glu Thr 195 200 205 Lys Glu Trp Glu GlyGln Ile Asp Asp His Gln Ser Ser Arg Leu Ser 210 215 220 Ser Ser Leu ThrVal Gln Gln Lys Ile Lys Ser Ala Thr Ile His Ala 225 230 235 240 Ala SerLys Val Phe Ile Thr Phe Glu Val Lys Gly Lys Glu Lys Arg 245 250 255 LysLys His Leu 260 31 1335 DNA Homo sapiens CDS (61)..(1332) 31 agtctcctctggagaaaata atctgtgaaa ttatgtgaat agagaccatt tttcaaaaca 60 atg ggg gaaaga gca gga agt cca ggt act gat caa gaa aga aag gca 108 Met Gly Glu ArgAla Gly Ser Pro Gly Thr Asp Gln Glu Arg Lys Ala 1 5 10 15 ggc aaa caccat tat tct tac tca tct gat ttt gaa acg cca cag tct 156 Gly Lys His HisTyr Ser Tyr Ser Ser Asp Phe Glu Thr Pro Gln Ser 20 25 30 tct ggc cga tcatcg ctg gtc agt tct tca cct gca agt gtt agg aga 204 Ser Gly Arg Ser SerLeu Val Ser Ser Ser Pro Ala Ser Val Arg Arg 35 40 45 aaa aat cct aaa agacaa act tca gat ggc caa gta cat cac cgg aaa 252 Lys Asn Pro Lys Arg GlnThr Ser Asp Gly Gln Val His His Arg Lys 50 55 60 cca agc cct aag ggt ctacca aac aga aag gga gtc cga gtg gga ttt 300 Pro Ser Pro Lys Gly Leu ProAsn Arg Lys Gly Val Arg Val Gly Phe 65 70 75 80 cgc tcc cag agc ctc aataga gag cca ctt cgg aaa gat act gat ctt 348 Arg Ser Gln Ser Leu Asn ArgGlu Pro Leu Arg Lys Asp Thr Asp Leu 85 90 95 gtt aca aaa cgg att ctg tctgca aga ctg cta aaa atc aat gag ttg 396 Val Thr Lys Arg Ile Leu Ser AlaArg Leu Leu Lys Ile Asn Glu Leu 100 105 110 cag aat gaa gta tct gaa ctccag gtc aag tta gct gag ctg cta aaa 444 Gln Asn Glu Val Ser Glu Leu GlnVal Lys Leu Ala Glu Leu Leu Lys 115 120 125 gaa aat aaa tct ttg aaa aggctt cag tac aga cag gag aaa gcc ctg 492 Glu Asn Lys Ser Leu Lys Arg LeuGln Tyr Arg Gln Glu Lys Ala Leu 130 135 140 aat aag ttt gaa gat gcc gaaaat gaa atc tca caa ctt ata ttt cgt 540 Asn Lys Phe Glu Asp Ala Glu AsnGlu Ile Ser Gln Leu Ile Phe Arg 145 150 155 160 cat aac aat gag att acagca ctc aaa gaa cgc tta aga aaa tct caa 588 His Asn Asn Glu Ile Thr AlaLeu Lys Glu Arg Leu Arg Lys Ser Gln 165 170 175 gag aaa gaa cgg gca actgag aaa agg gta aaa gat aca gaa agt gaa 636 Glu Lys Glu Arg Ala Thr GluLys Arg Val Lys Asp Thr Glu Ser Glu 180 185 190 cta ttt agg aca aaa ttttcc tta cag aaa ctg aaa gag atc tct gaa 684 Leu Phe Arg Thr Lys Phe SerLeu Gln Lys Leu Lys Glu Ile Ser Glu 195 200 205 gct aga cac cta cct gaacga gat gat ttg gca aag aaa cta gtt tca 732 Ala Arg His Leu Pro Glu ArgAsp Asp Leu Ala Lys Lys Leu Val Ser 210 215 220 gca gag tta aag tta gatgac acc gag aga aga att aag gag cta tcg 780 Ala Glu Leu Lys Leu Asp AspThr Glu Arg Arg Ile Lys Glu Leu Ser 225 230 235 240 aaa aac ctt gaa ctgagt act aac agt ttc caa cga cag ttg ctt gct 828 Lys Asn Leu Glu Leu SerThr Asn Ser Phe Gln Arg Gln Leu Leu Ala 245 250 255 gaa agg aaa agg gcatat gag gct cat gat gaa aat aaa gtt ctt caa 876 Glu Arg Lys Arg Ala TyrGlu Ala His Asp Glu Asn Lys Val Leu Gln 260 265 270 aag gag gta cag cgacta tat cac aaa tta aag gaa aag gag aga gaa 924 Lys Glu Val Gln Arg LeuTyr His Lys Leu Lys Glu Lys Glu Arg Glu 275 280 285 ctg gat ata aaa aatata tat tct aat cgt ctg cca aag tcc tct cca 972 Leu Asp Ile Lys Asn IleTyr Ser Asn Arg Leu Pro Lys Ser Ser Pro 290 295 300 aat aaa gag aaa gaactt gca tta aga aaa aat gca tgc cag agt gat 1020 Asn Lys Glu Lys Glu LeuAla Leu Arg Lys Asn Ala Cys Gln Ser Asp 305 310 315 320 ttt gca gac ctgtgt aca aaa gga gta caa acc atg gaa gac ttc aag 1068 Phe Ala Asp Leu CysThr Lys Gly Val Gln Thr Met Glu Asp Phe Lys 325 330 335 cca gaa gaa tatcct tta act cca gaa aca att atg tgt tac gaa aac 1116 Pro Glu Glu Tyr ProLeu Thr Pro Glu Thr Ile Met Cys Tyr Glu Asn 340 345 350 aaa tgg gaa gaacca gga cat ctt act ttg caa tct caa aag caa gac 1164 Lys Trp Glu Glu ProGly His Leu Thr Leu Gln Ser Gln Lys Gln Asp 355 360 365 agg cat gga gaagca ggg att cta aac cca att atg gaa aga gaa gaa 1212 Arg His Gly Glu AlaGly Ile Leu Asn Pro Ile Met Glu Arg Glu Glu 370 375 380 aaa ttt gtt acagat gaa gaa ctc cat gtc gta aaa cag gag gtt gaa 1260 Lys Phe Val Thr AspGlu Glu Leu His Val Val Lys Gln Glu Val Glu 385 390 395 400 aag ctg gaggat ggt aag aaa aag agt ttg ttt aag cat gtg aca agt 1308 Lys Leu Glu AspGly Lys Lys Lys Ser Leu Phe Lys His Val Thr Ser 405 410 415 cag cat cccttg aga aag aaa gag tga 1335 Gln His Pro Leu Arg Lys Lys Glu 420 32 424PRT Homo sapiens 32 Met Gly Glu Arg Ala Gly Ser Pro Gly Thr Asp Gln GluArg Lys Ala 1 5 10 15 Gly Lys His His Tyr Ser Tyr Ser Ser Asp Phe GluThr Pro Gln Ser 20 25 30 Ser Gly Arg Ser Ser Leu Val Ser Ser Ser Pro AlaSer Val Arg Arg 35 40 45 Lys Asn Pro Lys Arg Gln Thr Ser Asp Gly Gln ValHis His Arg Lys 50 55 60 Pro Ser Pro Lys Gly Leu Pro Asn Arg Lys Gly ValArg Val Gly Phe 65 70 75 80 Arg Ser Gln Ser Leu Asn Arg Glu Pro Leu ArgLys Asp Thr Asp Leu 85 90 95 Val Thr Lys Arg Ile Leu Ser Ala Arg Leu LeuLys Ile Asn Glu Leu 100 105 110 Gln Asn Glu Val Ser Glu Leu Gln Val LysLeu Ala Glu Leu Leu Lys 115 120 125 Glu Asn Lys Ser Leu Lys Arg Leu GlnTyr Arg Gln Glu Lys Ala Leu 130 135 140 Asn Lys Phe Glu Asp Ala Glu AsnGlu Ile Ser Gln Leu Ile Phe Arg 145 150 155 160 His Asn Asn Glu Ile ThrAla Leu Lys Glu Arg Leu Arg Lys Ser Gln 165 170 175 Glu Lys Glu Arg AlaThr Glu Lys Arg Val Lys Asp Thr Glu Ser Glu 180 185 190 Leu Phe Arg ThrLys Phe Ser Leu Gln Lys Leu Lys Glu Ile Ser Glu 195 200 205 Ala Arg HisLeu Pro Glu Arg Asp Asp Leu Ala Lys Lys Leu Val Ser 210 215 220 Ala GluLeu Lys Leu Asp Asp Thr Glu Arg Arg Ile Lys Glu Leu Ser 225 230 235 240Lys Asn Leu Glu Leu Ser Thr Asn Ser Phe Gln Arg Gln Leu Leu Ala 245 250255 Glu Arg Lys Arg Ala Tyr Glu Ala His Asp Glu Asn Lys Val Leu Gln 260265 270 Lys Glu Val Gln Arg Leu Tyr His Lys Leu Lys Glu Lys Glu Arg Glu275 280 285 Leu Asp Ile Lys Asn Ile Tyr Ser Asn Arg Leu Pro Lys Ser SerPro 290 295 300 Asn Lys Glu Lys Glu Leu Ala Leu Arg Lys Asn Ala Cys GlnSer Asp 305 310 315 320 Phe Ala Asp Leu Cys Thr Lys Gly Val Gln Thr MetGlu Asp Phe Lys 325 330 335 Pro Glu Glu Tyr Pro Leu Thr Pro Glu Thr IleMet Cys Tyr Glu Asn 340 345 350 Lys Trp Glu Glu Pro Gly His Leu Thr LeuGln Ser Gln Lys Gln Asp 355 360 365 Arg His Gly Glu Ala Gly Ile Leu AsnPro Ile Met Glu Arg Glu Glu 370 375 380 Lys Phe Val Thr Asp Glu Glu LeuHis Val Val Lys Gln Glu Val Glu 385 390 395 400 Lys Leu Glu Asp Gly LysLys Lys Ser Leu Phe Lys His Val Thr Ser 405 410 415 Gln His Pro Leu ArgLys Lys Glu 420 33 2071 DNA Homo sapiens CDS (263)..(2011) 33 actctcctcccccgagcggc agcggcagcg gcggcggcgg cggctgctgc gggcgctgaa 60 tgagagacggtgactgttcg ggtcgacgag tgctactcta ggcggcggcg gccgtggcgg 120 tgaagcgtgaggccggcatc gtctttccgt cctctgaggc gacggccgcg gctgcacagg 180 aataatgtatttgtggcctt ggacatgagg cagtcagtcc tctgttgctg ttaacataag 240 gtcagggactgatgaggaaa gc atg gac cta atg aac ggg cag gca agc agt 292 Met Asp LeuMet Asn Gly Gln Ala Ser Ser 1 5 10 gtc aat att gca gct act gct tct gagaaa agt agc agc tct gaa tcc 340 Val Asn Ile Ala Ala Thr Ala Ser Glu LysSer Ser Ser Ser Glu Ser 15 20 25 tta agt gac aaa ggc tct gaa ttg aag aaaagc ttt gat gct gtg gta 388 Leu Ser Asp Lys Gly Ser Glu Leu Lys Lys SerPhe Asp Ala Val Val 30 35 40 ttc gat gtt ctt aag gtt aca cca gaa gaa tatgcg ggt cag ata aca 436 Phe Asp Val Leu Lys Val Thr Pro Glu Glu Tyr AlaGly Gln Ile Thr 45 50 55 tta atg gat gtt cca gta ttt aaa gct att caa ccagat gag ctt tca 484 Leu Met Asp Val Pro Val Phe Lys Ala Ile Gln Pro AspGlu Leu Ser 60 65 70 agt tgt gga tgg aat aaa aaa gaa aaa tat agt tct gcacca aat gca 532 Ser Cys Gly Trp Asn Lys Lys Glu Lys Tyr Ser Ser Ala ProAsn Ala 75 80 85 90 gtt gcc ttc aca aga aga ttc aat cat gta agc ttt tgggtt gtt aga 580 Val Ala Phe Thr Arg Arg Phe Asn His Val Ser Phe Trp ValVal Arg 95 100 105 gag att ctt cat gct caa aca tta aaa att aga gca gaagtt ttg agc 628 Glu Ile Leu His Ala Gln Thr Leu Lys Ile Arg Ala Glu ValLeu Ser 110 115 120 cac tat att aaa act gct aag aaa ctg tat gag ctg aataac ctt cat 676 His Tyr Ile Lys Thr Ala Lys Lys Leu Tyr Glu Leu Asn AsnLeu His 125 130 135 gca ctt atg gca gtg gtt tct ggc cta cag agt gcc ccaatt ttc agg 724 Ala Leu Met Ala Val Val Ser Gly Leu Gln Ser Ala Pro IlePhe Arg 140 145 150 ttg act aaa aca tgg gcg tta tta agt cga aaa gac aaaact acc ttt 772 Leu Thr Lys Thr Trp Ala Leu Leu Ser Arg Lys Asp Lys ThrThr Phe 155 160 165 170 gaa aaa tta gaa tat gta atg agt aaa gaa gat aactac aaa aga ctc 820 Glu Lys Leu Glu Tyr Val Met Ser Lys Glu Asp Asn TyrLys Arg Leu 175 180 185 aga gac tat ata agt agc tta aag atg aca cct tgcatt ccc tat tta 868 Arg Asp Tyr Ile Ser Ser Leu Lys Met Thr Pro Cys IlePro Tyr Leu 190 195 200 ggt atc tat ttg tca gat tta aca tac atc gat tcagca tac cca tca 916 Gly Ile Tyr Leu Ser Asp Leu Thr Tyr Ile Asp Ser AlaTyr Pro Ser 205 210 215 act ggc agc att cta gaa aat gag caa aga tca aattta atg aat aat 964 Thr Gly Ser Ile Leu Glu Asn Glu Gln Arg Ser Asn LeuMet Asn Asn 220 225 230 atc ctt cga ata att tct gat tta cag cag tct tgtgaa tat gat att 1012 Ile Leu Arg Ile Ile Ser Asp Leu Gln Gln Ser Cys GluTyr Asp Ile 235 240 245 250 ccc atg ttg cct cat gtc caa aaa tat ctc aactct gtt cag tat ata 1060 Pro Met Leu Pro His Val Gln Lys Tyr Leu Asn SerVal Gln Tyr Ile 255 260 265 gaa gaa cta caa aaa ttt gtg gaa gac gat aattac aag ctt tca tta 1108 Glu Glu Leu Gln Lys Phe Val Glu Asp Asp Asn TyrLys Leu Ser Leu 270 275 280 aag ata gaa cca ggg aca agc acc cca cgt tctgct gct tcc aga gaa 1156 Lys Ile Glu Pro Gly Thr Ser Thr Pro Arg Ser AlaAla Ser Arg Glu 285 290 295 gat tta gta ggt cct gaa gta gga gcg tct ccacag agt gga cga aaa 1204 Asp Leu Val Gly Pro Glu Val Gly Ala Ser Pro GlnSer Gly Arg Lys 300 305 310 agt gtg gca gct gaa gga gcc ttg ctc cca cagaca ccg cca tcc cct 1252 Ser Val Ala Ala Glu Gly Ala Leu Leu Pro Gln ThrPro Pro Ser Pro 315 320 325 330 cgg aat ctg att cca cat gga cat agg aagtgc cat agt ttg ggt tat 1300 Arg Asn Leu Ile Pro His Gly His Arg Lys CysHis Ser Leu Gly Tyr 335 340 345 aat ttc att cat aaa atg aac aca gca gaattt aag agt gca acg ttt 1348 Asn Phe Ile His Lys Met Asn Thr Ala Glu PheLys Ser Ala Thr Phe 350 355 360 cca aat gca gga cca aga cat ctg tta gatgat agc gtc atg gag ccc 1396 Pro Asn Ala Gly Pro Arg His Leu Leu Asp AspSer Val Met Glu Pro 365 370 375 cat gcg cca tct cga ggc caa gct gaa agttct act ctt tct agt gga 1444 His Ala Pro Ser Arg Gly Gln Ala Glu Ser SerThr Leu Ser Ser Gly 380 385 390 ata tca ata ggt agc agc gat ggt tct gaacta agt gaa gag acc tca 1492 Ile Ser Ile Gly Ser Ser Asp Gly Ser Glu LeuSer Glu Glu Thr Ser 395 400 405 410 tgg cct gct ttt gaa agg aac aga ttatac cat tct ctc ggc ccg gtg 1540 Trp Pro Ala Phe Glu Arg Asn Arg Leu TyrHis Ser Leu Gly Pro Val 415 420 425 aca aga gtg gca cga aat ggc tat cgaagt cac atg aag gcc agc agt 1588 Thr Arg Val Ala Arg Asn Gly Tyr Arg SerHis Met Lys Ala Ser Ser 430 435 440 tct gca gaa tca gaa gat ttg gca gtacat tta tat cca gga gct gtt 1636 Ser Ala Glu Ser Glu Asp Leu Ala Val HisLeu Tyr Pro Gly Ala Val 445 450 455 act att caa ggt gtt ctc agg aga aaaact ttg tta aaa gaa ggc aaa 1684 Thr Ile Gln Gly Val Leu Arg Arg Lys ThrLeu Leu Lys Glu Gly Lys 460 465 470 aag cct aca gta gca tct tgg aca aaatat tgg gca gct ttg tgt ggg 1732 Lys Pro Thr Val Ala Ser Trp Thr Lys TyrTrp Ala Ala Leu Cys Gly 475 480 485 490 aca cag ctt ttt tac tat gct gccaaa tct cta aag gct acc gaa aga 1780 Thr Gln Leu Phe Tyr Tyr Ala Ala LysSer Leu Lys Ala Thr Glu Arg 495 500 505 aaa cat ttc aaa tca aca tcc aataag aac gta tct gtg ata gga tgg 1828 Lys His Phe Lys Ser Thr Ser Asn LysAsn Val Ser Val Ile Gly Trp 510 515 520 atg gtg atg atg gct gat gac cctgaa cat cct gat ctc ttc ctg ctg 1876 Met Val Met Met Ala Asp Asp Pro GluHis Pro Asp Leu Phe Leu Leu 525 530 535 act gac tct gag aaa gga aat tcgtac aag ttt caa gct ggc aat aga 1924 Thr Asp Ser Glu Lys Gly Asn Ser TyrLys Phe Gln Ala Gly Asn Arg 540 545 550 atg aat gca atg tta tgg ttt aagcat ttg agt gca gcc tgc caa agt 1972 Met Asn Ala Met Leu Trp Phe Lys HisLeu Ser Ala Ala Cys Gln Ser 555 560 565 570 aac aaa caa cag gtt cct acaaac ttg atg act ttt gag tagaagcctg 2021 Asn Lys Gln Gln Val Pro Thr AsnLeu Met Thr Phe Glu 575 580 agaaaaaaag agaggtgaac tgttgcttct acgtgagcatgaggacctga 2071 34 583 PRT Homo sapiens 34 Met Asp Leu Met Asn Gly GlnAla Ser Ser Val Asn Ile Ala Ala Thr 1 5 10 15 Ala Ser Glu Lys Ser SerSer Ser Glu Ser Leu Ser Asp Lys Gly Ser 20 25 30 Glu Leu Lys Lys Ser PheAsp Ala Val Val Phe Asp Val Leu Lys Val 35 40 45 Thr Pro Glu Glu Tyr AlaGly Gln Ile Thr Leu Met Asp Val Pro Val 50 55 60 Phe Lys Ala Ile Gln ProAsp Glu Leu Ser Ser Cys Gly Trp Asn Lys 65 70 75 80 Lys Glu Lys Tyr SerSer Ala Pro Asn Ala Val Ala Phe Thr Arg Arg 85 90 95 Phe Asn His Val SerPhe Trp Val Val Arg Glu Ile Leu His Ala Gln 100 105 110 Thr Leu Lys IleArg Ala Glu Val Leu Ser His Tyr Ile Lys Thr Ala 115 120 125 Lys Lys LeuTyr Glu Leu Asn Asn Leu His Ala Leu Met Ala Val Val 130 135 140 Ser GlyLeu Gln Ser Ala Pro Ile Phe Arg Leu Thr Lys Thr Trp Ala 145 150 155 160Leu Leu Ser Arg Lys Asp Lys Thr Thr Phe Glu Lys Leu Glu Tyr Val 165 170175 Met Ser Lys Glu Asp Asn Tyr Lys Arg Leu Arg Asp Tyr Ile Ser Ser 180185 190 Leu Lys Met Thr Pro Cys Ile Pro Tyr Leu Gly Ile Tyr Leu Ser Asp195 200 205 Leu Thr Tyr Ile Asp Ser Ala Tyr Pro Ser Thr Gly Ser Ile LeuGlu 210 215 220 Asn Glu Gln Arg Ser Asn Leu Met Asn Asn Ile Leu Arg IleIle Ser 225 230 235 240 Asp Leu Gln Gln Ser Cys Glu Tyr Asp Ile Pro MetLeu Pro His Val 245 250 255 Gln Lys Tyr Leu Asn Ser Val Gln Tyr Ile GluGlu Leu Gln Lys Phe 260 265 270 Val Glu Asp Asp Asn Tyr Lys Leu Ser LeuLys Ile Glu Pro Gly Thr 275 280 285 Ser Thr Pro Arg Ser Ala Ala Ser ArgGlu Asp Leu Val Gly Pro Glu 290 295 300 Val Gly Ala Ser Pro Gln Ser GlyArg Lys Ser Val Ala Ala Glu Gly 305 310 315 320 Ala Leu Leu Pro Gln ThrPro Pro Ser Pro Arg Asn Leu Ile Pro His 325 330 335 Gly His Arg Lys CysHis Ser Leu Gly Tyr Asn Phe Ile His Lys Met 340 345 350 Asn Thr Ala GluPhe Lys Ser Ala Thr Phe Pro Asn Ala Gly Pro Arg 355 360 365 His Leu LeuAsp Asp Ser Val Met Glu Pro His Ala Pro Ser Arg Gly 370 375 380 Gln AlaGlu Ser Ser Thr Leu Ser Ser Gly Ile Ser Ile Gly Ser Ser 385 390 395 400Asp Gly Ser Glu Leu Ser Glu Glu Thr Ser Trp Pro Ala Phe Glu Arg 405 410415 Asn Arg Leu Tyr His Ser Leu Gly Pro Val Thr Arg Val Ala Arg Asn 420425 430 Gly Tyr Arg Ser His Met Lys Ala Ser Ser Ser Ala Glu Ser Glu Asp435 440 445 Leu Ala Val His Leu Tyr Pro Gly Ala Val Thr Ile Gln Gly ValLeu 450 455 460 Arg Arg Lys Thr Leu Leu Lys Glu Gly Lys Lys Pro Thr ValAla Ser 465 470 475 480 Trp Thr Lys Tyr Trp Ala Ala Leu Cys Gly Thr GlnLeu Phe Tyr Tyr 485 490 495 Ala Ala Lys Ser Leu Lys Ala Thr Glu Arg LysHis Phe Lys Ser Thr 500 505 510 Ser Asn Lys Asn Val Ser Val Ile Gly TrpMet Val Met Met Ala Asp 515 520 525 Asp Pro Glu His Pro Asp Leu Phe LeuLeu Thr Asp Ser Glu Lys Gly 530 535 540 Asn Ser Tyr Lys Phe Gln Ala GlyAsn Arg Met Asn Ala Met Leu Trp 545 550 555 560 Phe Lys His Leu Ser AlaAla Cys Gln Ser Asn Lys Gln Gln Val Pro 565 570 575 Thr Asn Leu Met ThrPhe Glu 580 35 1513 DNA Homo sapiens CDS (1)..(1488) 35 atg ggg aag gccccg agg gtc cct gtg ccc cca gca ggg ctc agc ctg 48 Met Gly Lys Ala ProArg Val Pro Val Pro Pro Ala Gly Leu Ser Leu 1 5 10 15 ccg ctc aaa gaccca cct gcc agc cag gcc gtg tcc ttg ctc acg gag 96 Pro Leu Lys Asp ProPro Ala Ser Gln Ala Val Ser Leu Leu Thr Glu 20 25 30 tac gcg gcc agc ctgggc atc ttc ctg ctc ttc cgg gag gac cag cca 144 Tyr Ala Ala Ser Leu GlyIle Phe Leu Leu Phe Arg Glu Asp Gln Pro 35 40 45 cca ggt gag gcc ggg ccgggg ttc ccc ttc tcg gtg agc gcg gaa ctg 192 Pro Gly Glu Ala Gly Pro GlyPhe Pro Phe Ser Val Ser Ala Glu Leu 50 55 60 gat ggg gtg gtc tgc cct gcgggc act gcg aat agc aag acg gag gcc 240 Asp Gly Val Val Cys Pro Ala GlyThr Ala Asn Ser Lys Thr Glu Ala 65 70 75 80 aaa cag cag gca gcg ctc tctgcc ctc tgc tac atc cgg agt cag ctg 288 Lys Gln Gln Ala Ala Leu Ser AlaLeu Cys Tyr Ile Arg Ser Gln Leu 85 90 95 gag aac cca ggt aat gga gtg ggcccc ctt cta cct gca gtc tct cgc 336 Glu Asn Pro Gly Asn Gly Val Gly ProLeu Leu Pro Ala Val Ser Arg 100 105 110 cct ggc gca gag aac atc ctg acccat gag cag cgc tgc gca gcg ttg 384 Pro Gly Ala Glu Asn Ile Leu Thr HisGlu Gln Arg Cys Ala Ala Leu 115 120 125 gtg agc gcc ggc ttt gac ctc ctgttg gac gag cgc tcg cca tac tgg 432 Val Ser Ala Gly Phe Asp Leu Leu LeuAsp Glu Arg Ser Pro Tyr Trp 130 135 140 gcc tgt aag ggg act gtg gct ggagtc atc ctg gag agg gag atc ccg 480 Ala Cys Lys Gly Thr Val Ala Gly ValIle Leu Glu Arg Glu Ile Pro 145 150 155 160 cgt gcc agg ggc cac gtg aaggag atc tac aag ctg gtg gct ctg ggc 528 Arg Ala Arg Gly His Val Lys GluIle Tyr Lys Leu Val Ala Leu Gly 165 170 175 acc ggc agc agc tgc tgt gctggc tgg ctg gag ttc tcg ggc cag cag 576 Thr Gly Ser Ser Cys Cys Ala GlyTrp Leu Glu Phe Ser Gly Gln Gln 180 185 190 ctc cac gac tgc cat ggc ctggtc atc gcc cgc agg gcc ctg ctg agg 624 Leu His Asp Cys His Gly Leu ValIle Ala Arg Arg Ala Leu Leu Arg 195 200 205 ttc ttg ttc cgg cag ctc ctgctg gcc aca cag ggg ggc ccc aag ggc 672 Phe Leu Phe Arg Gln Leu Leu LeuAla Thr Gln Gly Gly Pro Lys Gly 210 215 220 aag gag cag tcc gtg ctg gccccc cag cca ggg ccc gga ccc cca ttc 720 Lys Glu Gln Ser Val Leu Ala ProGln Pro Gly Pro Gly Pro Pro Phe 225 230 235 240 acc ctc aag ccc cgc gtcttc ctg cac ctc tac atc agc aac acc ccc 768 Thr Leu Lys Pro Arg Val PheLeu His Leu Tyr Ile Ser Asn Thr Pro 245 250 255 aag ggc gcg gcc cgt gacatc aag tat gca ggg ccc tcg gaa ggt ggc 816 Lys Gly Ala Ala Arg Asp IleLys Tyr Ala Gly Pro Ser Glu Gly Gly 260 265 270 ctc ccg cac agc cca cccatg cgc ctg cag gcc cat gtg ctc ggg cag 864 Leu Pro His Ser Pro Pro MetArg Leu Gln Ala His Val Leu Gly Gln 275 280 285 ctg aag cct gtg tgc tacgtg gcg ccc tcg ctc tgt gac acc cac gtg 912 Leu Lys Pro Val Cys Tyr ValAla Pro Ser Leu Cys Asp Thr His Val 290 295 300 ggc tgc ctg tca gcc agtgac aag ctg gca cgc tgg gcc gtg ctg ggg 960 Gly Cys Leu Ser Ala Ser AspLys Leu Ala Arg Trp Ala Val Leu Gly 305 310 315 320 ctg ggt ggt gcc ctgctg gcc cac ctg gtg tcc cca ctc tac agc acc 1008 Leu Gly Gly Ala Leu LeuAla His Leu Val Ser Pro Leu Tyr Ser Thr 325 330 335 agc ctc atc ctg gctgac tca tgc cac gac cct ccg act ctg agc agg 1056 Ser Leu Ile Leu Ala AspSer Cys His Asp Pro Pro Thr Leu Ser Arg 340 345 350 gcc atc cac acc cggccc tgc ctg gac agt gtc ctg ggg cca tgc ctg 1104 Ala Ile His Thr Arg ProCys Leu Asp Ser Val Leu Gly Pro Cys Leu 355 360 365 cca cct ccc tac gtccgg acc gcc ctg cac ctg ttt gca ggg ccc ccg 1152 Pro Pro Pro Tyr Val ArgThr Ala Leu His Leu Phe Ala Gly Pro Pro 370 375 380 gtg gcc cct tcc gaaccc acc cct gac acc tgc cgt ggc ctg agc ctc 1200 Val Ala Pro Ser Glu ProThr Pro Asp Thr Cys Arg Gly Leu Ser Leu 385 390 395 400 aac tgg agc ctgggg gac cct ggc atc gag gtt gtg gat gtg gcc acc 1248 Asn Trp Ser Leu GlyAsp Pro Gly Ile Glu Val Val Asp Val Ala Thr 405 410 415 ggg cgt gtg aagtcc agt gcc gcc ctg ggg cct ccc tcc cgt ctc tgc 1296 Gly Arg Val Lys SerSer Ala Ala Leu Gly Pro Pro Ser Arg Leu Cys 420 425 430 aag gcc tcc tttctc cgg gcc ttt cac cag gcg gcc agg gct gtg ggg 1344 Lys Ala Ser Phe LeuArg Ala Phe His Gln Ala Ala Arg Ala Val Gly 435 440 445 aag ccc tac ctcctg gcc ttg aag acc tac gag gct gcc aag gct ggg 1392 Lys Pro Tyr Leu LeuAla Leu Lys Thr Tyr Glu Ala Ala Lys Ala Gly 450 455 460 ccc tac cag gaggct cgc agg cag ctg tct ctc ctc ctg gac cag cag 1440 Pro Tyr Gln Glu AlaArg Arg Gln Leu Ser Leu Leu Leu Asp Gln Gln 465 470 475 480 ggc ctg ggggct tgg ccc tcg aag cca ctg gtg ggc aaa ttc aga aac 1488 Gly Leu Gly AlaTrp Pro Ser Lys Pro Leu Val Gly Lys Phe Arg Asn 485 490 495 tgaagccagcctcggcggga ccgag 1513 36 496 PRT Homo sapiens 36 Met Gly Lys Ala Pro ArgVal Pro Val Pro Pro Ala Gly Leu Ser Leu 1 5 10 15 Pro Leu Lys Asp ProPro Ala Ser Gln Ala Val Ser Leu Leu Thr Glu 20 25 30 Tyr Ala Ala Ser LeuGly Ile Phe Leu Leu Phe Arg Glu Asp Gln Pro 35 40 45 Pro Gly Glu Ala GlyPro Gly Phe Pro Phe Ser Val Ser Ala Glu Leu 50 55 60 Asp Gly Val Val CysPro Ala Gly Thr Ala Asn Ser Lys Thr Glu Ala 65 70 75 80 Lys Gln Gln AlaAla Leu Ser Ala Leu Cys Tyr Ile Arg Ser Gln Leu 85 90 95 Glu Asn Pro GlyAsn Gly Val Gly Pro Leu Leu Pro Ala Val Ser Arg 100 105 110 Pro Gly AlaGlu Asn Ile Leu Thr His Glu Gln Arg Cys Ala Ala Leu 115 120 125 Val SerAla Gly Phe Asp Leu Leu Leu Asp Glu Arg Ser Pro Tyr Trp 130 135 140 AlaCys Lys Gly Thr Val Ala Gly Val Ile Leu Glu Arg Glu Ile Pro 145 150 155160 Arg Ala Arg Gly His Val Lys Glu Ile Tyr Lys Leu Val Ala Leu Gly 165170 175 Thr Gly Ser Ser Cys Cys Ala Gly Trp Leu Glu Phe Ser Gly Gln Gln180 185 190 Leu His Asp Cys His Gly Leu Val Ile Ala Arg Arg Ala Leu LeuArg 195 200 205 Phe Leu Phe Arg Gln Leu Leu Leu Ala Thr Gln Gly Gly ProLys Gly 210 215 220 Lys Glu Gln Ser Val Leu Ala Pro Gln Pro Gly Pro GlyPro Pro Phe 225 230 235 240 Thr Leu Lys Pro Arg Val Phe Leu His Leu TyrIle Ser Asn Thr Pro 245 250 255 Lys Gly Ala Ala Arg Asp Ile Lys Tyr AlaGly Pro Ser Glu Gly Gly 260 265 270 Leu Pro His Ser Pro Pro Met Arg LeuGln Ala His Val Leu Gly Gln 275 280 285 Leu Lys Pro Val Cys Tyr Val AlaPro Ser Leu Cys Asp Thr His Val 290 295 300 Gly Cys Leu Ser Ala Ser AspLys Leu Ala Arg Trp Ala Val Leu Gly 305 310 315 320 Leu Gly Gly Ala LeuLeu Ala His Leu Val Ser Pro Leu Tyr Ser Thr 325 330 335 Ser Leu Ile LeuAla Asp Ser Cys His Asp Pro Pro Thr Leu Ser Arg 340 345 350 Ala Ile HisThr Arg Pro Cys Leu Asp Ser Val Leu Gly Pro Cys Leu 355 360 365 Pro ProPro Tyr Val Arg Thr Ala Leu His Leu Phe Ala Gly Pro Pro 370 375 380 ValAla Pro Ser Glu Pro Thr Pro Asp Thr Cys Arg Gly Leu Ser Leu 385 390 395400 Asn Trp Ser Leu Gly Asp Pro Gly Ile Glu Val Val Asp Val Ala Thr 405410 415 Gly Arg Val Lys Ser Ser Ala Ala Leu Gly Pro Pro Ser Arg Leu Cys420 425 430 Lys Ala Ser Phe Leu Arg Ala Phe His Gln Ala Ala Arg Ala ValGly 435 440 445 Lys Pro Tyr Leu Leu Ala Leu Lys Thr Tyr Glu Ala Ala LysAla Gly 450 455 460 Pro Tyr Gln Glu Ala Arg Arg Gln Leu Ser Leu Leu LeuAsp Gln Gln 465 470 475 480 Gly Leu Gly Ala Trp Pro Ser Lys Pro Leu ValGly Lys Phe Arg Asn 485 490 495 37 1754 DNA Homo sapiens CDS(58)..(1737) 37 ttaaaaatca tctttgatta ttcttctttt ctagtaaaat aatatttagaaaaaata 57 atg tca gag cac agc aga aat tca gat caa gaa gaa ctt ctc gatgag 105 Met Ser Glu His Ser Arg Asn Ser Asp Gln Glu Glu Leu Leu Asp Glu1 5 10 15 gag att aat gaa gat gaa atc ttg gcc aac ttg tct gct gaa gaactg 153 Glu Ile Asn Glu Asp Glu Ile Leu Ala Asn Leu Ser Ala Glu Glu Leu20 25 30 aaa gaa ctg cag tcg gaa atg gaa gtc atg gcc cct gac ccc agc ctt201 Lys Glu Leu Gln Ser Glu Met Glu Val Met Ala Pro Asp Pro Ser Leu 3540 45 ccc gtg gga atg att cag aaa gat caa act gac aag cca ccg aca gga249 Pro Val Gly Met Ile Gln Lys Asp Gln Thr Asp Lys Pro Pro Thr Gly 5055 60 aac ttc aat cat aaa tct ctt gtt gat tat atg tat tgg gaa aag gca297 Asn Phe Asn His Lys Ser Leu Val Asp Tyr Met Tyr Trp Glu Lys Ala 6570 75 80 tcc agg cgc atg ctg gaa gag gaa cga gtt cct gtc acc ttt gtg aaa345 Ser Arg Arg Met Leu Glu Glu Glu Arg Val Pro Val Thr Phe Val Lys 8590 95 tcc gag gaa aag act caa gaa gag cat gaa gaa ata gaa aaa cgt aat393 Ser Glu Glu Lys Thr Gln Glu Glu His Glu Glu Ile Glu Lys Arg Asn 100105 110 aaa aat atg gcc cag tat tta aaa gaa aag ctc aat aat gaa ata gtt441 Lys Asn Met Ala Gln Tyr Leu Lys Glu Lys Leu Asn Asn Glu Ile Val 115120 125 gca aat aaa aga gaa tca aag ggc agc agc aat atc caa gaa aca gat489 Ala Asn Lys Arg Glu Ser Lys Gly Ser Ser Asn Ile Gln Glu Thr Asp 130135 140 gaa gaa gat gaa gaa gaa gaa gat gat gat gat gac gac gaa gga gaa537 Glu Glu Asp Glu Glu Glu Glu Asp Asp Asp Asp Asp Asp Glu Gly Glu 145150 155 160 gat gat ggt gaa gag agt gaa gaa acg aac aga gaa gag gaa ggcaaa 585 Asp Asp Gly Glu Glu Ser Glu Glu Thr Asn Arg Glu Glu Glu Gly Lys165 170 175 gca aag gaa caa att aga aat tgt gag aac aac tgc cag cag gtaact 633 Ala Lys Glu Gln Ile Arg Asn Cys Glu Asn Asn Cys Gln Gln Val Thr180 185 190 gac aaa gca ttc aaa gaa cag aga gac aga cca gag gcc caa gaacaa 681 Asp Lys Ala Phe Lys Glu Gln Arg Asp Arg Pro Glu Ala Gln Glu Gln195 200 205 agt gag aaa aaa ata tcg aaa tta gat cct aag aag tta gct ctagac 729 Ser Glu Lys Lys Ile Ser Lys Leu Asp Pro Lys Lys Leu Ala Leu Asp210 215 220 acc agc ttt ttg aag gta agt aca agg cct tca gga aac cag acagac 777 Thr Ser Phe Leu Lys Val Ser Thr Arg Pro Ser Gly Asn Gln Thr Asp225 230 235 240 ctg gat ggg agc ttg agg aga gtt agg aaa aat gat cct gacatg aag 825 Leu Asp Gly Ser Leu Arg Arg Val Arg Lys Asn Asp Pro Asp MetLys 245 250 255 gaa ctc aac ctg aac aac att gaa aac atc ccc aaa gaa atgtta ctg 873 Glu Leu Asn Leu Asn Asn Ile Glu Asn Ile Pro Lys Glu Met LeuLeu 260 265 270 gac ttt gtc aat gca atg aag aaa aac aag cac atc aaa acattc agt 921 Asp Phe Val Asn Ala Met Lys Lys Asn Lys His Ile Lys Thr PheSer 275 280 285 tta gcc aat gtg ggt gca gat gag aat gta gca ttt gcc ttggct aac 969 Leu Ala Asn Val Gly Ala Asp Glu Asn Val Ala Phe Ala Leu AlaAsn 290 295 300 atg ttg cgt gaa aat aga agc atc acc act ctc aac atc gagtcc aat 1017 Met Leu Arg Glu Asn Arg Ser Ile Thr Thr Leu Asn Ile Glu SerAsn 305 310 315 320 ttc atc aca ggt aaa ggg att gtg gcc atc atg agg tgtctc cag ttt 1065 Phe Ile Thr Gly Lys Gly Ile Val Ala Ile Met Arg Cys LeuGln Phe 325 330 335 aat gag acg cta act gag ctt cgg ttt cac aat cag aggcac atg ttg 1113 Asn Glu Thr Leu Thr Glu Leu Arg Phe His Asn Gln Arg HisMet Leu 340 345 350 ggt cac cat gct gaa atg gaa ata gcc agg ctt ttg aaggca aac aac 1161 Gly His His Ala Glu Met Glu Ile Ala Arg Leu Leu Lys AlaAsn Asn 355 360 365 act ctc ctg aag atg ggc tac cat ttt gag ctt ccg ggtccc aga atg 1209 Thr Leu Leu Lys Met Gly Tyr His Phe Glu Leu Pro Gly ProArg Met 370 375 380 gtg gtc act aat ctg ctc acc agg aat cag gat aaa caaagg cag aaa 1257 Val Val Thr Asn Leu Leu Thr Arg Asn Gln Asp Lys Gln ArgGln Lys 385 390 395 400 cga cag gaa gag caa aaa cag cag caa ctc aag gaacag aag aag ctg 1305 Arg Gln Glu Glu Gln Lys Gln Gln Gln Leu Lys Glu GlnLys Lys Leu 405 410 415 ata gcc atg tta gag aat ggg ttg ggg ctg ccc cctggg atg tgg gag 1353 Ile Ala Met Leu Glu Asn Gly Leu Gly Leu Pro Pro GlyMet Trp Glu 420 425 430 ctg ttg gga gga ccc aag cca gat tcc aga atg caggaa ttc ttc cag 1401 Leu Leu Gly Gly Pro Lys Pro Asp Ser Arg Met Gln GluPhe Phe Gln 435 440 445 cca ccg cca cct cgg cct ccc aac ccc caa aat gtcccc ttt agt caa 1449 Pro Pro Pro Pro Arg Pro Pro Asn Pro Gln Asn Val ProPhe Ser Gln 450 455 460 cgc agt gaa atg atg aaa aag cca tcg cag gcc ccgaag tac agg aca 1497 Arg Ser Glu Met Met Lys Lys Pro Ser Gln Ala Pro LysTyr Arg Thr 465 470 475 480 gac cct gac tcc ttc cgg gtg gtg aag ctg aagaga atc cag cgc aaa 1545 Asp Pro Asp Ser Phe Arg Val Val Lys Leu Lys ArgIle Gln Arg Lys 485 490 495 tct cgg atg ccg gaa gcc aga gaa cca ccc gagaaa acc aac ctc aaa 1593 Ser Arg Met Pro Glu Ala Arg Glu Pro Pro Glu LysThr Asn Leu Lys 500 505 510 gat gtc atc aaa acg ctc aag cca gtg ccg agaaac agg cca ccc cca 1641 Asp Val Ile Lys Thr Leu Lys Pro Val Pro Arg AsnArg Pro Pro Pro 515 520 525 ttg gtg gaa atc act ccc aga gat cag ctg ctaaac gac att cgt cac 1689 Leu Val Glu Ile Thr Pro Arg Asp Gln Leu Leu AsnAsp Ile Arg His 530 535 540 agc agt gtc gcc tat ctt aaa cct gta agt agaagg agg gag aaa tgg 1737 Ser Ser Val Ala Tyr Leu Lys Pro Val Ser Arg ArgArg Glu Lys Trp 545 550 555 560 tgactgagca ccctcca 1754 38 560 PRT Homosapiens 38 Met Ser Glu His Ser Arg Asn Ser Asp Gln Glu Glu Leu Leu AspGlu 1 5 10 15 Glu Ile Asn Glu Asp Glu Ile Leu Ala Asn Leu Ser Ala GluGlu Leu 20 25 30 Lys Glu Leu Gln Ser Glu Met Glu Val Met Ala Pro Asp ProSer Leu 35 40 45 Pro Val Gly Met Ile Gln Lys Asp Gln Thr Asp Lys Pro ProThr Gly 50 55 60 Asn Phe Asn His Lys Ser Leu Val Asp Tyr Met Tyr Trp GluLys Ala 65 70 75 80 Ser Arg Arg Met Leu Glu Glu Glu Arg Val Pro Val ThrPhe Val Lys 85 90 95 Ser Glu Glu Lys Thr Gln Glu Glu His Glu Glu Ile GluLys Arg Asn 100 105 110 Lys Asn Met Ala Gln Tyr Leu Lys Glu Lys Leu AsnAsn Glu Ile Val 115 120 125 Ala Asn Lys Arg Glu Ser Lys Gly Ser Ser AsnIle Gln Glu Thr Asp 130 135 140 Glu Glu Asp Glu Glu Glu Glu Asp Asp AspAsp Asp Asp Glu Gly Glu 145 150 155 160 Asp Asp Gly Glu Glu Ser Glu GluThr Asn Arg Glu Glu Glu Gly Lys 165 170 175 Ala Lys Glu Gln Ile Arg AsnCys Glu Asn Asn Cys Gln Gln Val Thr 180 185 190 Asp Lys Ala Phe Lys GluGln Arg Asp Arg Pro Glu Ala Gln Glu Gln 195 200 205 Ser Glu Lys Lys IleSer Lys Leu Asp Pro Lys Lys Leu Ala Leu Asp 210 215 220 Thr Ser Phe LeuLys Val Ser Thr Arg Pro Ser Gly Asn Gln Thr Asp 225 230 235 240 Leu AspGly Ser Leu Arg Arg Val Arg Lys Asn Asp Pro Asp Met Lys 245 250 255 GluLeu Asn Leu Asn Asn Ile Glu Asn Ile Pro Lys Glu Met Leu Leu 260 265 270Asp Phe Val Asn Ala Met Lys Lys Asn Lys His Ile Lys Thr Phe Ser 275 280285 Leu Ala Asn Val Gly Ala Asp Glu Asn Val Ala Phe Ala Leu Ala Asn 290295 300 Met Leu Arg Glu Asn Arg Ser Ile Thr Thr Leu Asn Ile Glu Ser Asn305 310 315 320 Phe Ile Thr Gly Lys Gly Ile Val Ala Ile Met Arg Cys LeuGln Phe 325 330 335 Asn Glu Thr Leu Thr Glu Leu Arg Phe His Asn Gln ArgHis Met Leu 340 345 350 Gly His His Ala Glu Met Glu Ile Ala Arg Leu LeuLys Ala Asn Asn 355 360 365 Thr Leu Leu Lys Met Gly Tyr His Phe Glu LeuPro Gly Pro Arg Met 370 375 380 Val Val Thr Asn Leu Leu Thr Arg Asn GlnAsp Lys Gln Arg Gln Lys 385 390 395 400 Arg Gln Glu Glu Gln Lys Gln GlnGln Leu Lys Glu Gln Lys Lys Leu 405 410 415 Ile Ala Met Leu Glu Asn GlyLeu Gly Leu Pro Pro Gly Met Trp Glu 420 425 430 Leu Leu Gly Gly Pro LysPro Asp Ser Arg Met Gln Glu Phe Phe Gln 435 440 445 Pro Pro Pro Pro ArgPro Pro Asn Pro Gln Asn Val Pro Phe Ser Gln 450 455 460 Arg Ser Glu MetMet Lys Lys Pro Ser Gln Ala Pro Lys Tyr Arg Thr 465 470 475 480 Asp ProAsp Ser Phe Arg Val Val Lys Leu Lys Arg Ile Gln Arg Lys 485 490 495 SerArg Met Pro Glu Ala Arg Glu Pro Pro Glu Lys Thr Asn Leu Lys 500 505 510Asp Val Ile Lys Thr Leu Lys Pro Val Pro Arg Asn Arg Pro Pro Pro 515 520525 Leu Val Glu Ile Thr Pro Arg Asp Gln Leu Leu Asn Asp Ile Arg His 530535 540 Ser Ser Val Ala Tyr Leu Lys Pro Val Ser Arg Arg Arg Glu Lys Trp545 550 555 560 39 2768 DNA Homo sapiens CDS (435)..(2708) 39 gcattgcatgtttgtttgcc attgcccccg ccaccctgca agttgcacct tctagaaaca 60 gcaagccaagctcctctcac ccagcgtaat gatgcggaaa tgcaaatgca ccatcatgtt 120 gtgacccatattgcgaaaat tagaaaaaag gaagttgtgt ttcgctattg cacgaagttc 180 agcccagaggagaaactcgc tcgccttcag aagacagtac ctcctaaatg gctctacttt 240 gaacctgctgggcaaggaag agattttcaa ggaaaccatc taccgtgtgc aagctcctgc 300 cggccaaccccagaccccag cacggagcca ggcgcctgtg cccgccaacc ctcagcatcc 360 tcctcagaaaggctggtggc atcaggaagc ccctggccag cctccacctg agcccagtga 420 gctcagctttaagg atg gag tca ggc agg ggg tcc tca acc cct cca gga 470 Met Glu Ser GlyArg Gly Ser Ser Thr Pro Pro Gly 1 5 10 ccc att gct gcc cta ggg atg ccagac act ggg cct ggc agt tcc tcc 518 Pro Ile Ala Ala Leu Gly Met Pro AspThr Gly Pro Gly Ser Ser Ser 15 20 25 cta ggg aag ctt cag gcg ctc cct gttggg ccc aga gcc cac tgt ggg 566 Leu Gly Lys Leu Gln Ala Leu Pro Val GlyPro Arg Ala His Cys Gly 30 35 40 gac cct gtc agc ctg gct gca gca ggg gacggc tct cca gac ata ggc 614 Asp Pro Val Ser Leu Ala Ala Ala Gly Asp GlySer Pro Asp Ile Gly 45 50 55 60 ccc acg gga gag ctg agt ggt agc tta aagatc ccc aac cgg gac agc 662 Pro Thr Gly Glu Leu Ser Gly Ser Leu Lys IlePro Asn Arg Asp Ser 65 70 75 ggg atc gac agt ccc tcc tcc agt gtg gct ggagag aac ttt ccc tgc 710 Gly Ile Asp Ser Pro Ser Ser Ser Val Ala Gly GluAsn Phe Pro Cys 80 85 90 gag gag ggc ttg gag gct ggc cca agc ccc act gtactg ggg gcg cac 758 Glu Glu Gly Leu Glu Ala Gly Pro Ser Pro Thr Val LeuGly Ala His 95 100 105 gca gag atg gcc ctg gac agc cag gtc ccg aag gtcacc ccc cag gag 806 Ala Glu Met Ala Leu Asp Ser Gln Val Pro Lys Val ThrPro Gln Glu 110 115 120 gag gcg gac agc gac gtg ggt gag gaa cct gac tctgag aac acc ccc 854 Glu Ala Asp Ser Asp Val Gly Glu Glu Pro Asp Ser GluAsn Thr Pro 125 130 135 140 cag aag gct gac aag gat gcc ggc ctg gcc cagcac tct ggc ccc cag 902 Gln Lys Ala Asp Lys Asp Ala Gly Leu Ala Gln HisSer Gly Pro Gln 145 150 155 aag ctt ctc cac att gcc cag gag ctc ctg cacacc gag gag acc tat 950 Lys Leu Leu His Ile Ala Gln Glu Leu Leu His ThrGlu Glu Thr Tyr 160 165 170 gtg aag cgg ctg cac ctg ctg gac cag gtt ttctgc acc agg ctg acg 998 Val Lys Arg Leu His Leu Leu Asp Gln Val Phe CysThr Arg Leu Thr 175 180 185 gat gcg ggg atc cct cca gaa gtc atc atg ggcata ttc tct aac atc 1046 Asp Ala Gly Ile Pro Pro Glu Val Ile Met Gly IlePhe Ser Asn Ile 190 195 200 tcc tcc atc cac cgc ttc cac ggg cag ttc ctgctg ccg gag ctg aag 1094 Ser Ser Ile His Arg Phe His Gly Gln Phe Leu LeuPro Glu Leu Lys 205 210 215 220 acg cgg atc acg gag gag tgg gac aca aaccca cgg ctc ggg gac atc 1142 Thr Arg Ile Thr Glu Glu Trp Asp Thr Asn ProArg Leu Gly Asp Ile 225 230 235 ctg cag aag ctg gcc cca ttc ctg aag atgtac ggc gag tat gtc aag 1190 Leu Gln Lys Leu Ala Pro Phe Leu Lys Met TyrGly Glu Tyr Val Lys 240 245 250 aac ttt gac cga gcc gta ggg ctg gtg agcacg tgg acc cag cgc tcc 1238 Asn Phe Asp Arg Ala Val Gly Leu Val Ser ThrTrp Thr Gln Arg Ser 255 260 265 cca ctg ttt aaa gac gtc gtc cac agc atccag aag cag gag gta tgc 1286 Pro Leu Phe Lys Asp Val Val His Ser Ile GlnLys Gln Glu Val Cys 270 275 280 ggg aac ctg acg ctg cag cac cac atg ctggag ccc gtg cag agg gtc 1334 Gly Asn Leu Thr Leu Gln His His Met Leu GluPro Val Gln Arg Val 285 290 295 300 ccc cgg tac gag ctg ctg ctc aag gactat ctg aag agg ctc ccg cag 1382 Pro Arg Tyr Glu Leu Leu Leu Lys Asp TyrLeu Lys Arg Leu Pro Gln 305 310 315 gac gcc cca gac cgg aag gat gcg gagagg tcc ttg gag ctc atc tcc 1430 Asp Ala Pro Asp Arg Lys Asp Ala Glu ArgSer Leu Glu Leu Ile Ser 320 325 330 aca gcc gcc aac cac tcc aat gct gccatt cgg aaa gtg gag aaa atg 1478 Thr Ala Ala Asn His Ser Asn Ala Ala IleArg Lys Val Glu Lys Met 335 340 345 cac aag ctc ttg gag gtg tac gag cagctg ggt ggg gaa gaa gac att 1526 His Lys Leu Leu Glu Val Tyr Glu Gln LeuGly Gly Glu Glu Asp Ile 350 355 360 gtc aac ccg gcc aat gaa ctg atc aaggag ggc caa atc cag aaa ctg 1574 Val Asn Pro Ala Asn Glu Leu Ile Lys GluGly Gln Ile Gln Lys Leu 365 370 375 380 tca gcc aag aac ggc acc ccc caggac cgc cac ctc ttc ctg ttc aac 1622 Ser Ala Lys Asn Gly Thr Pro Gln AspArg His Leu Phe Leu Phe Asn 385 390 395 agc atg atc ctt tac tgt gtg cccaag ctg cgg ctc atg ggc cag aag 1670 Ser Met Ile Leu Tyr Cys Val Pro LysLeu Arg Leu Met Gly Gln Lys 400 405 410 ttc agc gtc cgg gag aag atg gacatc tca ggc ctc cag gtg cag gat 1718 Phe Ser Val Arg Glu Lys Met Asp IleSer Gly Leu Gln Val Gln Asp 415 420 425 atc gtc aag cca aac aca gca cataca ttc atc ata aca gga aga aaa 1766 Ile Val Lys Pro Asn Thr Ala His ThrPhe Ile Ile Thr Gly Arg Lys 430 435 440 agg tcc ctg gag ctg cag acg cggaca gag gaa gag aag aaa gaa tgg 1814 Arg Ser Leu Glu Leu Gln Thr Arg ThrGlu Glu Glu Lys Lys Glu Trp 445 450 455 460 att cag atc atc cag gcc accatc gag aag cac aaa cag aac agc gaa 1862 Ile Gln Ile Ile Gln Ala Thr IleGlu Lys His Lys Gln Asn Ser Glu 465 470 475 acc ttc aag gct ttt ggt ggcgcc ttc agc cag gat gag gac ccc agc 1910 Thr Phe Lys Ala Phe Gly Gly AlaPhe Ser Gln Asp Glu Asp Pro Ser 480 485 490 ctc tct cca gac atg cct atcacg agc acc agc cct gtg gag cct gtg 1958 Leu Ser Pro Asp Met Pro Ile ThrSer Thr Ser Pro Val Glu Pro Val 495 500 505 gtg acc acc gaa ggc agt tcgggt gca gca ggg ctc gag ccc aga aaa 2006 Val Thr Thr Glu Gly Ser Ser GlyAla Ala Gly Leu Glu Pro Arg Lys 510 515 520 cta tcc tct aag acc aga cgtgac aag gag aag cag agc tgt aag agc 2054 Leu Ser Ser Lys Thr Arg Arg AspLys Glu Lys Gln Ser Cys Lys Ser 525 530 535 540 tgt ggt gag acc ttc aactcc atc acc aag agg agg cat cac tgc aag 2102 Cys Gly Glu Thr Phe Asn SerIle Thr Lys Arg Arg His His Cys Lys 545 550 555 ctg tgt ggg gcg gtc atctgt ggg aag tgc tcc gag ttc aag gcc gag 2150 Leu Cys Gly Ala Val Ile CysGly Lys Cys Ser Glu Phe Lys Ala Glu 560 565 570 aac agc cgg cag agc cgtgtc tgc aga gat tgt ttc ctg aca cag cca 2198 Asn Ser Arg Gln Ser Arg ValCys Arg Asp Cys Phe Leu Thr Gln Pro 575 580 585 gtg gcc cct gag agc acagag gtg ggt gct ccc agc tcc tgc tcc cct 2246 Val Ala Pro Glu Ser Thr GluVal Gly Ala Pro Ser Ser Cys Ser Pro 590 595 600 cct ggt ggc gcg gca gagcct cca gac acc tgc tcc tgt gcc cca gca 2294 Pro Gly Gly Ala Ala Glu ProPro Asp Thr Cys Ser Cys Ala Pro Ala 605 610 615 620 gct cca gct gcc tctgct ttc gga aag aca ccc act gca gac ccc cag 2342 Ala Pro Ala Ala Ser AlaPhe Gly Lys Thr Pro Thr Ala Asp Pro Gln 625 630 635 ccc agc ctg ctc tgcggc ccc ctg cgg ctg tca gag agc ggt gag acc 2390 Pro Ser Leu Leu Cys GlyPro Leu Arg Leu Ser Glu Ser Gly Glu Thr 640 645 650 tgg agc gag gtg tgggcc gcc atc ccc atg tca gat ccc cag gtg ctg 2438 Trp Ser Glu Val Trp AlaAla Ile Pro Met Ser Asp Pro Gln Val Leu 655 660 665 cac ctg cag gga ggcagc cag gac ggc cgg ctg ccc cgc acc atc cct 2486 His Leu Gln Gly Gly SerGln Asp Gly Arg Leu Pro Arg Thr Ile Pro 670 675 680 ctc ccc agc tgc aaactg agt gtg ccg gac cct gag gag agg ctg gac 2534 Leu Pro Ser Cys Lys LeuSer Val Pro Asp Pro Glu Glu Arg Leu Asp 685 690 695 700 tcg ggg cat gtgtgg aag ctg cag tgg gcc aag cag tcc tgg tac ctg 2582 Ser Gly His Val TrpLys Leu Gln Trp Ala Lys Gln Ser Trp Tyr Leu 705 710 715 agc gcc tcc tccgca gag ctg cag cag cag tgg ctg gaa acc cta agc 2630 Ser Ala Ser Ser AlaGlu Leu Gln Gln Gln Trp Leu Glu Thr Leu Ser 720 725 730 act gct gcc catggg gac acg gcc cag gac agc ccg ggg gcc ctg cag 2678 Thr Ala Ala His GlyAsp Thr Ala Gln Asp Ser Pro Gly Ala Leu Gln 735 740 745 ctt cag gtc cctatg ggc gca gct gct ccg tgagctgagt ctcccactgc 2728 Leu Gln Val Pro MetGly Ala Ala Ala Pro 750 755 cctgcacacc accacattgg acctgtgctg tcctgggagg2768 40 758 PRT Homo sapiens 40 Met Glu Ser Gly Arg Gly Ser Ser Thr ProPro Gly Pro Ile Ala Ala 1 5 10 15 Leu Gly Met Pro Asp Thr Gly Pro GlySer Ser Ser Leu Gly Lys Leu 20 25 30 Gln Ala Leu Pro Val Gly Pro Arg AlaHis Cys Gly Asp Pro Val Ser 35 40 45 Leu Ala Ala Ala Gly Asp Gly Ser ProAsp Ile Gly Pro Thr Gly Glu 50 55 60 Leu Ser Gly Ser Leu Lys Ile Pro AsnArg Asp Ser Gly Ile Asp Ser 65 70 75 80 Pro Ser Ser Ser Val Ala Gly GluAsn Phe Pro Cys Glu Glu Gly Leu 85 90 95 Glu Ala Gly Pro Ser Pro Thr ValLeu Gly Ala His Ala Glu Met Ala 100 105 110 Leu Asp Ser Gln Val Pro LysVal Thr Pro Gln Glu Glu Ala Asp Ser 115 120 125 Asp Val Gly Glu Glu ProAsp Ser Glu Asn Thr Pro Gln Lys Ala Asp 130 135 140 Lys Asp Ala Gly LeuAla Gln His Ser Gly Pro Gln Lys Leu Leu His 145 150 155 160 Ile Ala GlnGlu Leu Leu His Thr Glu Glu Thr Tyr Val Lys Arg Leu 165 170 175 His LeuLeu Asp Gln Val Phe Cys Thr Arg Leu Thr Asp Ala Gly Ile 180 185 190 ProPro Glu Val Ile Met Gly Ile Phe Ser Asn Ile Ser Ser Ile His 195 200 205Arg Phe His Gly Gln Phe Leu Leu Pro Glu Leu Lys Thr Arg Ile Thr 210 215220 Glu Glu Trp Asp Thr Asn Pro Arg Leu Gly Asp Ile Leu Gln Lys Leu 225230 235 240 Ala Pro Phe Leu Lys Met Tyr Gly Glu Tyr Val Lys Asn Phe AspArg 245 250 255 Ala Val Gly Leu Val Ser Thr Trp Thr Gln Arg Ser Pro LeuPhe Lys 260 265 270 Asp Val Val His Ser Ile Gln Lys Gln Glu Val Cys GlyAsn Leu Thr 275 280 285 Leu Gln His His Met Leu Glu Pro Val Gln Arg ValPro Arg Tyr Glu 290 295 300 Leu Leu Leu Lys Asp Tyr Leu Lys Arg Leu ProGln Asp Ala Pro Asp 305 310 315 320 Arg Lys Asp Ala Glu Arg Ser Leu GluLeu Ile Ser Thr Ala Ala Asn 325 330 335 His Ser Asn Ala Ala Ile Arg LysVal Glu Lys Met His Lys Leu Leu 340 345 350 Glu Val Tyr Glu Gln Leu GlyGly Glu Glu Asp Ile Val Asn Pro Ala 355 360 365 Asn Glu Leu Ile Lys GluGly Gln Ile Gln Lys Leu Ser Ala Lys Asn 370 375 380 Gly Thr Pro Gln AspArg His Leu Phe Leu Phe Asn Ser Met Ile Leu 385 390 395 400 Tyr Cys ValPro Lys Leu Arg Leu Met Gly Gln Lys Phe Ser Val Arg 405 410 415 Glu LysMet Asp Ile Ser Gly Leu Gln Val Gln Asp Ile Val Lys Pro 420 425 430 AsnThr Ala His Thr Phe Ile Ile Thr Gly Arg Lys Arg Ser Leu Glu 435 440 445Leu Gln Thr Arg Thr Glu Glu Glu Lys Lys Glu Trp Ile Gln Ile Ile 450 455460 Gln Ala Thr Ile Glu Lys His Lys Gln Asn Ser Glu Thr Phe Lys Ala 465470 475 480 Phe Gly Gly Ala Phe Ser Gln Asp Glu Asp Pro Ser Leu Ser ProAsp 485 490 495 Met Pro Ile Thr Ser Thr Ser Pro Val Glu Pro Val Val ThrThr Glu 500 505 510 Gly Ser Ser Gly Ala Ala Gly Leu Glu Pro Arg Lys LeuSer Ser Lys 515 520 525 Thr Arg Arg Asp Lys Glu Lys Gln Ser Cys Lys SerCys Gly Glu Thr 530 535 540 Phe Asn Ser Ile Thr Lys Arg Arg His His CysLys Leu Cys Gly Ala 545 550 555 560 Val Ile Cys Gly Lys Cys Ser Glu PheLys Ala Glu Asn Ser Arg Gln 565 570 575 Ser Arg Val Cys Arg Asp Cys PheLeu Thr Gln Pro Val Ala Pro Glu 580 585 590 Ser Thr Glu Val Gly Ala ProSer Ser Cys Ser Pro Pro Gly Gly Ala 595 600 605 Ala Glu Pro Pro Asp ThrCys Ser Cys Ala Pro Ala Ala Pro Ala Ala 610 615 620 Ser Ala Phe Gly LysThr Pro Thr Ala Asp Pro Gln Pro Ser Leu Leu 625 630 635 640 Cys Gly ProLeu Arg Leu Ser Glu Ser Gly Glu Thr Trp Ser Glu Val 645 650 655 Trp AlaAla Ile Pro Met Ser Asp Pro Gln Val Leu His Leu Gln Gly 660 665 670 GlySer Gln Asp Gly Arg Leu Pro Arg Thr Ile Pro Leu Pro Ser Cys 675 680 685Lys Leu Ser Val Pro Asp Pro Glu Glu Arg Leu Asp Ser Gly His Val 690 695700 Trp Lys Leu Gln Trp Ala Lys Gln Ser Trp Tyr Leu Ser Ala Ser Ser 705710 715 720 Ala Glu Leu Gln Gln Gln Trp Leu Glu Thr Leu Ser Thr Ala AlaHis 725 730 735 Gly Asp Thr Ala Gln Asp Ser Pro Gly Ala Leu Gln Leu GlnVal Pro 740 745 750 Met Gly Ala Ala Ala Pro 755 41 1944 DNA Homo sapiensCDS (61)..(1629) 41 cagcccgcga caactcgcgc cagctacggg gcctcagagaagccggactt cgcaagcacc 60 atg cag tgg ata agg ggc gga tcg gga atg ctg atcact gga gat tcc 108 Met Gln Trp Ile Arg Gly Gly Ser Gly Met Leu Ile ThrGly Asp Ser 1 5 10 15 atc gtt agt gct gag gca gta tgg gat cac gtc accatg gcc aac cgg 156 Ile Val Ser Ala Glu Ala Val Trp Asp His Val Thr MetAla Asn Arg 20 25 30 gag ttg gca ttt aaa gct ggc gac gtc atc aaa gtc ttggat gct tcc 204 Glu Leu Ala Phe Lys Ala Gly Asp Val Ile Lys Val Leu AspAla Ser 35 40 45 aac aag gat tgg tgg tgg ggc cag atc gac gat gag gag ggatgg ttt 252 Asn Lys Asp Trp Trp Trp Gly Gln Ile Asp Asp Glu Glu Gly TrpPhe 50 55 60 cct gcc agc ttt gtg agg ctc tgg gtg aac cag gag gat gag gtggag 300 Pro Ala Ser Phe Val Arg Leu Trp Val Asn Gln Glu Asp Glu Val Glu65 70 75 80 gag ggg ccc agc gat gtg cag aac gga cac ctg gac ccc aat tcagac 348 Glu Gly Pro Ser Asp Val Gln Asn Gly His Leu Asp Pro Asn Ser Asp85 90 95 tgc ctc tgt ctg ggg cgg cca cta cag aac cgg gac cag atg cgg gcc396 Cys Leu Cys Leu Gly Arg Pro Leu Gln Asn Arg Asp Gln Met Arg Ala 100105 110 aat gtc atc aat gag ata atg agc act gag cgt cac tac atc aag cac444 Asn Val Ile Asn Glu Ile Met Ser Thr Glu Arg His Tyr Ile Lys His 115120 125 ctc aag gat att tgt gag ggc tat ctg aag cag tgc cgg aag aga agg492 Leu Lys Asp Ile Cys Glu Gly Tyr Leu Lys Gln Cys Arg Lys Arg Arg 130135 140 gac atg ttc agt gac gag caa ctg aag gta atc ttt ggg aac att gaa540 Asp Met Phe Ser Asp Glu Gln Leu Lys Val Ile Phe Gly Asn Ile Glu 145150 155 160 gat atc tac aga ttt cag atg ggc ttt gtg aga gac ctg gag aaacag 588 Asp Ile Tyr Arg Phe Gln Met Gly Phe Val Arg Asp Leu Glu Lys Gln165 170 175 tat aac aat gat gac ccc cac ctc agc gag ata gga ccc tgc ttccta 636 Tyr Asn Asn Asp Asp Pro His Leu Ser Glu Ile Gly Pro Cys Phe Leu180 185 190 gag cac caa gat gga ttc tgg ata tac tct gag tat tgt aac aaccac 684 Glu His Gln Asp Gly Phe Trp Ile Tyr Ser Glu Tyr Cys Asn Asn His195 200 205 ctg gat gct tgc atg gag ctc tcc aaa ctg atg aag gac agc cgctac 732 Leu Asp Ala Cys Met Glu Leu Ser Lys Leu Met Lys Asp Ser Arg Tyr210 215 220 cag cac ttc ttt gag gcc tgt cgc ctc ttg cag cag atg att gacatt 780 Gln His Phe Phe Glu Ala Cys Arg Leu Leu Gln Gln Met Ile Asp Ile225 230 235 240 gct atc gat ggt ttc ctt ttg act cca gtg cag aag atc tgcaag tat 828 Ala Ile Asp Gly Phe Leu Leu Thr Pro Val Gln Lys Ile Cys LysTyr 245 250 255 ccc tta cag ttg gct gag ctc cta aag tat act gcc caa gaccac agt 876 Pro Leu Gln Leu Ala Glu Leu Leu Lys Tyr Thr Ala Gln Asp HisSer 260 265 270 gac tac agg tat gtg gca gct gct ttg gct gtc atg aga aatgtg act 924 Asp Tyr Arg Tyr Val Ala Ala Ala Leu Ala Val Met Arg Asn ValThr 275 280 285 cag cag atc aac gaa cgc aag cga cgt tta gag aat att gacaag att 972 Gln Gln Ile Asn Glu Arg Lys Arg Arg Leu Glu Asn Ile Asp LysIle 290 295 300 gct cag tgg cag gct tct gtc cta gac tgg gag ggc gag gacatc cta 1020 Ala Gln Trp Gln Ala Ser Val Leu Asp Trp Glu Gly Glu Asp IleLeu 305 310 315 320 gac agg agc tcg gag ctg atc tac act ggg gag atg gcctgg atc tac 1068 Asp Arg Ser Ser Glu Leu Ile Tyr Thr Gly Glu Met Ala TrpIle Tyr 325 330 335 cag ccc tac ggc cgc aac cag cag cgg gtc ttc ttc ctgttt gac cac 1116 Gln Pro Tyr Gly Arg Asn Gln Gln Arg Val Phe Phe Leu PheAsp His 340 345 350 cag atg gtc ctc tgc aag aag gac cta atc cgg aga gacatc ctg tac 1164 Gln Met Val Leu Cys Lys Lys Asp Leu Ile Arg Arg Asp IleLeu Tyr 355 360 365 tac aaa ggc cgc att gac atg gat aaa tat gag gta gttgac att gag 1212 Tyr Lys Gly Arg Ile Asp Met Asp Lys Tyr Glu Val Val AspIle Glu 370 375 380 gat ggc aga gat gat gac ttc aat gtc agc atg aag aatgcc ttt aag 1260 Asp Gly Arg Asp Asp Asp Phe Asn Val Ser Met Lys Asn AlaPhe Lys 385 390 395 400 ctt cac aac aag gag act gag gag ata cat ctg ttcttt gcc aag aag 1308 Leu His Asn Lys Glu Thr Glu Glu Ile His Leu Phe PheAla Lys Lys 405 410 415 ctg gag gaa aaa ata cgc tgg ctc agg gct ttc agagaa gag agg aaa 1356 Leu Glu Glu Lys Ile Arg Trp Leu Arg Ala Phe Arg GluGlu Arg Lys 420 425 430 atg gta cag gaa gat gaa aaa att ggc ttt gaa atttct gaa aac cag 1404 Met Val Gln Glu Asp Glu Lys Ile Gly Phe Glu Ile SerGlu Asn Gln 435 440 445 aag agg cag gct gca atg act gtg aga aaa gtc cctaag caa aaa ggt 1452 Lys Arg Gln Ala Ala Met Thr Val Arg Lys Val Pro LysGln Lys Gly 450 455 460 gtc aac tct gcc cgc tca gtt cct cct tcc tac ccacca ccg cag gac 1500 Val Asn Ser Ala Arg Ser Val Pro Pro Ser Tyr Pro ProPro Gln Asp 465 470 475 480 ccg tta aac cac ggc cag tac ctg gtc ccc gacggc atc gct cag tcg 1548 Pro Leu Asn His Gly Gln Tyr Leu Val Pro Asp GlyIle Ala Gln Ser 485 490 495 cag gtc ttt gag ttc acc gaa ccc aag cgc agccag tca cca ttc tgg 1596 Gln Val Phe Glu Phe Thr Glu Pro Lys Arg Ser GlnSer Pro Phe Trp 500 505 510 caa aac ttc agc agg tta acc ccc ttc aaa aaatgatacctac agggaggcag 1649 Gln Asn Phe Ser Arg Leu Thr Pro Phe Lys Lys515 520 ataattttaa aataaagtaa ataaaattat aatagatgga ccttttttcggagaagcact 1709 gttgaaattt atacacacac acacacacag agacccttga gtacacatacacacacacac 1769 acacagacac acacacacac acacacacac acacacacac agagagataaggaacaaaag 1829 tgttttctgt tgttttgggg aagtgaaata tgtggttggt aggaagaggtaccaatgact 1889 tccaaacatg tgattccgtc ttaaaagttt tccattttta ccctgtcccccttcc 1944 42 523 PRT Homo sapiens 42 Met Gln Trp Ile Arg Gly Gly SerGly Met Leu Ile Thr Gly Asp Ser 1 5 10 15 Ile Val Ser Ala Glu Ala ValTrp Asp His Val Thr Met Ala Asn Arg 20 25 30 Glu Leu Ala Phe Lys Ala GlyAsp Val Ile Lys Val Leu Asp Ala Ser 35 40 45 Asn Lys Asp Trp Trp Trp GlyGln Ile Asp Asp Glu Glu Gly Trp Phe 50 55 60 Pro Ala Ser Phe Val Arg LeuTrp Val Asn Gln Glu Asp Glu Val Glu 65 70 75 80 Glu Gly Pro Ser Asp ValGln Asn Gly His Leu Asp Pro Asn Ser Asp 85 90 95 Cys Leu Cys Leu Gly ArgPro Leu Gln Asn Arg Asp Gln Met Arg Ala 100 105 110 Asn Val Ile Asn GluIle Met Ser Thr Glu Arg His Tyr Ile Lys His 115 120 125 Leu Lys Asp IleCys Glu Gly Tyr Leu Lys Gln Cys Arg Lys Arg Arg 130 135 140 Asp Met PheSer Asp Glu Gln Leu Lys Val Ile Phe Gly Asn Ile Glu 145 150 155 160 AspIle Tyr Arg Phe Gln Met Gly Phe Val Arg Asp Leu Glu Lys Gln 165 170 175Tyr Asn Asn Asp Asp Pro His Leu Ser Glu Ile Gly Pro Cys Phe Leu 180 185190 Glu His Gln Asp Gly Phe Trp Ile Tyr Ser Glu Tyr Cys Asn Asn His 195200 205 Leu Asp Ala Cys Met Glu Leu Ser Lys Leu Met Lys Asp Ser Arg Tyr210 215 220 Gln His Phe Phe Glu Ala Cys Arg Leu Leu Gln Gln Met Ile AspIle 225 230 235 240 Ala Ile Asp Gly Phe Leu Leu Thr Pro Val Gln Lys IleCys Lys Tyr 245 250 255 Pro Leu Gln Leu Ala Glu Leu Leu Lys Tyr Thr AlaGln Asp His Ser 260 265 270 Asp Tyr Arg Tyr Val Ala Ala Ala Leu Ala ValMet Arg Asn Val Thr 275 280 285 Gln Gln Ile Asn Glu Arg Lys Arg Arg LeuGlu Asn Ile Asp Lys Ile 290 295 300 Ala Gln Trp Gln Ala Ser Val Leu AspTrp Glu Gly Glu Asp Ile Leu 305 310 315 320 Asp Arg Ser Ser Glu Leu IleTyr Thr Gly Glu Met Ala Trp Ile Tyr 325 330 335 Gln Pro Tyr Gly Arg AsnGln Gln Arg Val Phe Phe Leu Phe Asp His 340 345 350 Gln Met Val Leu CysLys Lys Asp Leu Ile Arg Arg Asp Ile Leu Tyr 355 360 365 Tyr Lys Gly ArgIle Asp Met Asp Lys Tyr Glu Val Val Asp Ile Glu 370 375 380 Asp Gly ArgAsp Asp Asp Phe Asn Val Ser Met Lys Asn Ala Phe Lys 385 390 395 400 LeuHis Asn Lys Glu Thr Glu Glu Ile His Leu Phe Phe Ala Lys Lys 405 410 415Leu Glu Glu Lys Ile Arg Trp Leu Arg Ala Phe Arg Glu Glu Arg Lys 420 425430 Met Val Gln Glu Asp Glu Lys Ile Gly Phe Glu Ile Ser Glu Asn Gln 435440 445 Lys Arg Gln Ala Ala Met Thr Val Arg Lys Val Pro Lys Gln Lys Gly450 455 460 Val Asn Ser Ala Arg Ser Val Pro Pro Ser Tyr Pro Pro Pro GlnAsp 465 470 475 480 Pro Leu Asn His Gly Gln Tyr Leu Val Pro Asp Gly IleAla Gln Ser 485 490 495 Gln Val Phe Glu Phe Thr Glu Pro Lys Arg Ser GlnSer Pro Phe Trp 500 505 510 Gln Asn Phe Ser Arg Leu Thr Pro Phe Lys Lys515 520 43 1359 DNA Homo sapiens CDS (31)..(1335) 43 gcgcccgaacccgcggcggc ggtggggacg atg tgg ttc ttt gcc cgg gac ccg 54 Met Trp Phe PheAla Arg Asp Pro 1 5 gtc cgg gac ttt ccg ttc gag ctc atc ccg gag ccc ccagag ggc ggc 102 Val Arg Asp Phe Pro Phe Glu Leu Ile Pro Glu Pro Pro GluGly Gly 10 15 20 ctg ccc ggg ccc tgg gcc ctg cac cgc ggc cgc aag aag gccaca ggc 150 Leu Pro Gly Pro Trp Ala Leu His Arg Gly Arg Lys Lys Ala ThrGly 25 30 35 40 agc ccc gtg tcc atc ttc gtc tat gat gtg aag cct ggc gcggaa gag 198 Ser Pro Val Ser Ile Phe Val Tyr Asp Val Lys Pro Gly Ala GluGlu 45 50 55 cag acc cag gtg gcc aaa gct gcc ttc aag cgc ttc aaa act ctacgg 246 Gln Thr Gln Val Ala Lys Ala Ala Phe Lys Arg Phe Lys Thr Leu Arg60 65 70 cac ccc aac atc ctg gct tac atc gat gga ctg gag aca gaa aaa tgc294 His Pro Asn Ile Leu Ala Tyr Ile Asp Gly Leu Glu Thr Glu Lys Cys 7580 85 ctc cac gtc gtg aca gag gct gtg acc ccg ttg gga ata tac ctc aag342 Leu His Val Val Thr Glu Ala Val Thr Pro Leu Gly Ile Tyr Leu Lys 9095 100 gcg aga gtg gag gct ggt ggc ctg aag gag ctg gag atc tcc tgg ggg390 Ala Arg Val Glu Ala Gly Gly Leu Lys Glu Leu Glu Ile Ser Trp Gly 105110 115 120 cta cac cag atc gtg aaa gcc ctc agc ttc ctg gtc aac gac tgcagc 438 Leu His Gln Ile Val Lys Ala Leu Ser Phe Leu Val Asn Asp Cys Ser125 130 135 ctc atc cac aac aat gtc tgc atg gcc gcc gtg ttc gtg gac cgagct 486 Leu Ile His Asn Asn Val Cys Met Ala Ala Val Phe Val Asp Arg Ala140 145 150 ggc gag tgg aag ctt ggg ggc ctg gac tac atg tat tcg gcc cagggc 534 Gly Glu Trp Lys Leu Gly Gly Leu Asp Tyr Met Tyr Ser Ala Gln Gly155 160 165 aac ggt ggg gga cct ccc cgc aag ggg atc ccc gag ctt gag cagtat 582 Asn Gly Gly Gly Pro Pro Arg Lys Gly Ile Pro Glu Leu Glu Gln Tyr170 175 180 gac ccc ccg gag ttg gct gac agc agt ggc aga gtg gtc aga gagaag 630 Asp Pro Pro Glu Leu Ala Asp Ser Ser Gly Arg Val Val Arg Glu Lys185 190 195 200 tgg tca gca gac atg tgg cgc ttg ggc tgc ctc att tgg gaagtc ttc 678 Trp Ser Ala Asp Met Trp Arg Leu Gly Cys Leu Ile Trp Glu ValPhe 205 210 215 aat ggg ccc cta cct cgg gca gca gcc cta cgc aac cct gggaag atc 726 Asn Gly Pro Leu Pro Arg Ala Ala Ala Leu Arg Asn Pro Gly LysIle 220 225 230 ccc aaa acg ctg gtg ccc cat tac tgt gag ctg gtg gga gcaaac ccc 774 Pro Lys Thr Leu Val Pro His Tyr Cys Glu Leu Val Gly Ala AsnPro 235 240 245 aag gtg cgt ccc aac cca gcc cgc ttc ctg cag aac tgc cgggca cct 822 Lys Val Arg Pro Asn Pro Ala Arg Phe Leu Gln Asn Cys Arg AlaPro 250 255 260 ggt ggc ttc atg agc aac cgc ttt gta gaa acc aac ctc ttcctg gag 870 Gly Gly Phe Met Ser Asn Arg Phe Val Glu Thr Asn Leu Phe LeuGlu 265 270 275 280 gag att cag atc aaa gag cca gcc gag aag caa aaa ttcttc cag gag 918 Glu Ile Gln Ile Lys Glu Pro Ala Glu Lys Gln Lys Phe PheGln Glu 285 290 295 ctg agc aag agc ctg gac gca ttc cct gag gat ttc tgtcgg cac aag 966 Leu Ser Lys Ser Leu Asp Ala Phe Pro Glu Asp Phe Cys ArgHis Lys 300 305 310 gtg ctg ccc cag ctg ctg acc gcc ttc gag ttc ggc aatgct ggg gcc 1014 Val Leu Pro Gln Leu Leu Thr Ala Phe Glu Phe Gly Asn AlaGly Ala 315 320 325 gtt gtc ctc acg ccc ctc ttc aag gtg ggc aag ttc ctgagc gct gag 1062 Val Val Leu Thr Pro Leu Phe Lys Val Gly Lys Phe Leu SerAla Glu 330 335 340 gag tat cag cag aag atc atc cct gtg gtg gtc aag atgttc tca tcc 1110 Glu Tyr Gln Gln Lys Ile Ile Pro Val Val Val Lys Met PheSer Ser 345 350 355 360 act gac cgg gcc atg cgc atc cgc ctc ctg cag cagatg gag cag ttc 1158 Thr Asp Arg Ala Met Arg Ile Arg Leu Leu Gln Gln MetGlu Gln Phe 365 370 375 atc cag tac ctt gac gag cca aca gtc aac acc cagatc ttc ccc cac 1206 Ile Gln Tyr Leu Asp Glu Pro Thr Val Asn Thr Gln IlePhe Pro His 380 385 390 gtc gtg cta gtc agg tca gca act ccg acc aca aatcct cca aat ccc 1254 Val Val Leu Val Arg Ser Ala Thr Pro Thr Thr Asn ProPro Asn Pro 395 400 405 cag agt ccg act gga gca gct ggg aag ctg agg gctcct ggg aac agg 1302 Gln Ser Pro Thr Gly Ala Ala Gly Lys Leu Arg Ala ProGly Asn Arg 410 415 420 gct ggc agg agc aag ctc cca gga gcc acc tcctgacggtaca cggctggcca 1355 Ala Gly Arg Ser Lys Leu Pro Gly Ala Thr Ser425 430 435 gcga 1359 44 435 PRT Homo sapiens 44 Met Trp Phe Phe Ala ArgAsp Pro Val Arg Asp Phe Pro Phe Glu Leu 1 5 10 15 Ile Pro Glu Pro ProGlu Gly Gly Leu Pro Gly Pro Trp Ala Leu His 20 25 30 Arg Gly Arg Lys LysAla Thr Gly Ser Pro Val Ser Ile Phe Val Tyr 35 40 45 Asp Val Lys Pro GlyAla Glu Glu Gln Thr Gln Val Ala Lys Ala Ala 50 55 60 Phe Lys Arg Phe LysThr Leu Arg His Pro Asn Ile Leu Ala Tyr Ile 65 70 75 80 Asp Gly Leu GluThr Glu Lys Cys Leu His Val Val Thr Glu Ala Val 85 90 95 Thr Pro Leu GlyIle Tyr Leu Lys Ala Arg Val Glu Ala Gly Gly Leu 100 105 110 Lys Glu LeuGlu Ile Ser Trp Gly Leu His Gln Ile Val Lys Ala Leu 115 120 125 Ser PheLeu Val Asn Asp Cys Ser Leu Ile His Asn Asn Val Cys Met 130 135 140 AlaAla Val Phe Val Asp Arg Ala Gly Glu Trp Lys Leu Gly Gly Leu 145 150 155160 Asp Tyr Met Tyr Ser Ala Gln Gly Asn Gly Gly Gly Pro Pro Arg Lys 165170 175 Gly Ile Pro Glu Leu Glu Gln Tyr Asp Pro Pro Glu Leu Ala Asp Ser180 185 190 Ser Gly Arg Val Val Arg Glu Lys Trp Ser Ala Asp Met Trp ArgLeu 195 200 205 Gly Cys Leu Ile Trp Glu Val Phe Asn Gly Pro Leu Pro ArgAla Ala 210 215 220 Ala Leu Arg Asn Pro Gly Lys Ile Pro Lys Thr Leu ValPro His Tyr 225 230 235 240 Cys Glu Leu Val Gly Ala Asn Pro Lys Val ArgPro Asn Pro Ala Arg 245 250 255 Phe Leu Gln Asn Cys Arg Ala Pro Gly GlyPhe Met Ser Asn Arg Phe 260 265 270 Val Glu Thr Asn Leu Phe Leu Glu GluIle Gln Ile Lys Glu Pro Ala 275 280 285 Glu Lys Gln Lys Phe Phe Gln GluLeu Ser Lys Ser Leu Asp Ala Phe 290 295 300 Pro Glu Asp Phe Cys Arg HisLys Val Leu Pro Gln Leu Leu Thr Ala 305 310 315 320 Phe Glu Phe Gly AsnAla Gly Ala Val Val Leu Thr Pro Leu Phe Lys 325 330 335 Val Gly Lys PheLeu Ser Ala Glu Glu Tyr Gln Gln Lys Ile Ile Pro 340 345 350 Val Val ValLys Met Phe Ser Ser Thr Asp Arg Ala Met Arg Ile Arg 355 360 365 Leu LeuGln Gln Met Glu Gln Phe Ile Gln Tyr Leu Asp Glu Pro Thr 370 375 380 ValAsn Thr Gln Ile Phe Pro His Val Val Leu Val Arg Ser Ala Thr 385 390 395400 Pro Thr Thr Asn Pro Pro Asn Pro Gln Ser Pro Thr Gly Ala Ala Gly 405410 415 Lys Leu Arg Ala Pro Gly Asn Arg Ala Gly Arg Ser Lys Leu Pro Gly420 425 430 Ala Thr Ser 435 45 1117 DNA Homo sapiens CDS (7)..(1107) 45cctgcc atg gcg gct tct gcg gcg gag acg cgc gtg ttt ctg gag gtg 48 MetAla Ala Ser Ala Ala Glu Thr Arg Val Phe Leu Glu Val 1 5 10 cgg gga cagctg cag agc gcg ctt ctg atc ctg ggg gaa ccg aaa gaa 96 Arg Gly Gln LeuGln Ser Ala Leu Leu Ile Leu Gly Glu Pro Lys Glu 15 20 25 30 gga ggt atgccc atg aat att tcc ata atg cca tct tca ctc cag atg 144 Gly Gly Met ProMet Asn Ile Ser Ile Met Pro Ser Ser Leu Gln Met 35 40 45 aaa acc cct gaaggc tgc aca gaa atc cag ctt cca gca gag gtc agg 192 Lys Thr Pro Glu GlyCys Thr Glu Ile Gln Leu Pro Ala Glu Val Arg 50 55 60 ctt gta cct tcc tcttgc cgt ggg cta cag ttt gtt gtt gga gat gga 240 Leu Val Pro Ser Ser CysArg Gly Leu Gln Phe Val Val Gly Asp Gly 65 70 75 ctg cac ctg cga ctg cagacg caa gca aaa att tca atg ttt aat caa 288 Leu His Leu Arg Leu Gln ThrGln Ala Lys Ile Ser Met Phe Asn Gln 80 85 90 agc tcg caa acc caa gaa tgttgc acg ttt tat tgc caa tcc tgc ggt 336 Ser Ser Gln Thr Gln Glu Cys CysThr Phe Tyr Cys Gln Ser Cys Gly 95 100 105 110 gaa gtc ata ata aaa gacagg aag ctc ctc agg gtg ctc cca ctg ccg 384 Glu Val Ile Ile Lys Asp ArgLys Leu Leu Arg Val Leu Pro Leu Pro 115 120 125 agt gag aac tgg gga gctcta gtt gga gaa tgg tgt tgt cat cct gac 432 Ser Glu Asn Trp Gly Ala LeuVal Gly Glu Trp Cys Cys His Pro Asp 130 135 140 ccc ttt gct aat aaa tcactt cat ccg caa gag aat gac tgt ttt att 480 Pro Phe Ala Asn Lys Ser LeuHis Pro Gln Glu Asn Asp Cys Phe Ile 145 150 155 gga gac tct ttc ttc ttggtg aat tta aga acc agt ttg tgg cag cag 528 Gly Asp Ser Phe Phe Leu ValAsn Leu Arg Thr Ser Leu Trp Gln Gln 160 165 170 gaa cca aag gca aat accaaa gta att tgt aag cgt tgc aag gta atg 576 Glu Pro Lys Ala Asn Thr LysVal Ile Cys Lys Arg Cys Lys Val Met 175 180 185 190 ttg gga gag acc gtgtca tca gaa acc acc aag ttt tat atg aca gag 624 Leu Gly Glu Thr Val SerSer Glu Thr Thr Lys Phe Tyr Met Thr Glu 195 200 205 ata att att cag tcatct gag agg agt ttt cct atc ata cca agg tct 672 Ile Ile Ile Gln Ser SerGlu Arg Ser Phe Pro Ile Ile Pro Arg Ser 210 215 220 tgg ttt gtc cag agcgtg atc gcc cag tgt ctg gtg cag ctc tcc tct 720 Trp Phe Val Gln Ser ValIle Ala Gln Cys Leu Val Gln Leu Ser Ser 225 230 235 gct aga agc act tttaga ttc acg att caa ggt cag gat gac aaa gtg 768 Ala Arg Ser Thr Phe ArgPhe Thr Ile Gln Gly Gln Asp Asp Lys Val 240 245 250 tat atc ttg cta tggctt tta aat tca gac agt ttg gtg att gaa tct 816 Tyr Ile Leu Leu Trp LeuLeu Asn Ser Asp Ser Leu Val Ile Glu Ser 255 260 265 270 ttg aga aat tccaaa tat atc aaa aaa ttc ccc ttg ttg gaa aac aca 864 Leu Arg Asn Ser LysTyr Ile Lys Lys Phe Pro Leu Leu Glu Asn Thr 275 280 285 ttc aaa gcc gattct agt tct gcc tgg agt gct gtc aag gtc ctc tac 912 Phe Lys Ala Asp SerSer Ser Ala Trp Ser Ala Val Lys Val Leu Tyr 290 295 300 cag cca tgc atcaaa agc agg aat gaa aag ctt gtc agc ttg tgg gaa 960 Gln Pro Cys Ile LysSer Arg Asn Glu Lys Leu Val Ser Leu Trp Glu 305 310 315 agt gac atc agcgtc cac ccg cta acc ctg ccc tct gca acc tgc ttg 1008 Ser Asp Ile Ser ValHis Pro Leu Thr Leu Pro Ser Ala Thr Cys Leu 320 325 330 gag ctg ctg ttgata ttg tca aag agt aat gcc aat ctg cct tca tcc 1056 Glu Leu Leu Leu IleLeu Ser Lys Ser Asn Ala Asn Leu Pro Ser Ser 335 340 345 350 ctt cgc cgtgtg aat tcc ttt cag gtg agc aat ggc ttc ttt tct agg 1104 Leu Arg Arg ValAsn Ser Phe Gln Val Ser Asn Gly Phe Phe Ser Arg 355 360 365 ccgtgatttctca 1117 Pro 46 367 PRT Homo sapiens 46 Met Ala Ala Ser Ala AlaGlu Thr Arg Val Phe Leu Glu Val Arg Gly 1 5 10 15 Gln Leu Gln Ser AlaLeu Leu Ile Leu Gly Glu Pro Lys Glu Gly Gly 20 25 30 Met Pro Met Asn IleSer Ile Met Pro Ser Ser Leu Gln Met Lys Thr 35 40 45 Pro Glu Gly Cys ThrGlu Ile Gln Leu Pro Ala Glu Val Arg Leu Val 50 55 60 Pro Ser Ser Cys ArgGly Leu Gln Phe Val Val Gly Asp Gly Leu His 65 70 75 80 Leu Arg Leu GlnThr Gln Ala Lys Ile Ser Met Phe Asn Gln Ser Ser 85 90 95 Gln Thr Gln GluCys Cys Thr Phe Tyr Cys Gln Ser Cys Gly Glu Val 100 105 110 Ile Ile LysAsp Arg Lys Leu Leu Arg Val Leu Pro Leu Pro Ser Glu 115 120 125 Asn TrpGly Ala Leu Val Gly Glu Trp Cys Cys His Pro Asp Pro Phe 130 135 140 AlaAsn Lys Ser Leu His Pro Gln Glu Asn Asp Cys Phe Ile Gly Asp 145 150 155160 Ser Phe Phe Leu Val Asn Leu Arg Thr Ser Leu Trp Gln Gln Glu Pro 165170 175 Lys Ala Asn Thr Lys Val Ile Cys Lys Arg Cys Lys Val Met Leu Gly180 185 190 Glu Thr Val Ser Ser Glu Thr Thr Lys Phe Tyr Met Thr Glu IleIle 195 200 205 Ile Gln Ser Ser Glu Arg Ser Phe Pro Ile Ile Pro Arg SerTrp Phe 210 215 220 Val Gln Ser Val Ile Ala Gln Cys Leu Val Gln Leu SerSer Ala Arg 225 230 235 240 Ser Thr Phe Arg Phe Thr Ile Gln Gly Gln AspAsp Lys Val Tyr Ile 245 250 255 Leu Leu Trp Leu Leu Asn Ser Asp Ser LeuVal Ile Glu Ser Leu Arg 260 265 270 Asn Ser Lys Tyr Ile Lys Lys Phe ProLeu Leu Glu Asn Thr Phe Lys 275 280 285 Ala Asp Ser Ser Ser Ala Trp SerAla Val Lys Val Leu Tyr Gln Pro 290 295 300 Cys Ile Lys Ser Arg Asn GluLys Leu Val Ser Leu Trp Glu Ser Asp 305 310 315 320 Ile Ser Val His ProLeu Thr Leu Pro Ser Ala Thr Cys Leu Glu Leu 325 330 335 Leu Leu Ile LeuSer Lys Ser Asn Ala Asn Leu Pro Ser Ser Leu Arg 340 345 350 Arg Val AsnSer Phe Gln Val Ser Asn Gly Phe Phe Ser Arg Pro 355 360 365 47 1191 DNAHomo sapiens CDS (7)..(1182) 47 cctgcc atg gcg gct tct gcg gcg gag acgcgc gtg ttt ctg gag gtg 48 Met Ala Ala Ser Ala Ala Glu Thr Arg Val PheLeu Glu Val 1 5 10 cgg gga cag ctg cag agc gcg ctt ctg atc ctg gga gaaccg aaa gaa 96 Arg Gly Gln Leu Gln Ser Ala Leu Leu Ile Leu Gly Glu ProLys Glu 15 20 25 30 gga ggt atg ccc atg aat att tcc ata atg cca tct tcactc cag atg 144 Gly Gly Met Pro Met Asn Ile Ser Ile Met Pro Ser Ser LeuGln Met 35 40 45 aaa acc cct gaa ggc tgc aca gaa atc cag ctt cca gca gaggtc agg 192 Lys Thr Pro Glu Gly Cys Thr Glu Ile Gln Leu Pro Ala Glu ValArg 50 55 60 ctt gta cct tcc tct tgc cgt ggg cta cag ttt gtt gtt gga gatgga 240 Leu Val Pro Ser Ser Cys Arg Gly Leu Gln Phe Val Val Gly Asp Gly65 70 75 ctg cac ctg cga ctg cag acg caa gca aaa tta ggc aca aaa ctg att288 Leu His Leu Arg Leu Gln Thr Gln Ala Lys Leu Gly Thr Lys Leu Ile 8085 90 tca atg ttt aat caa agc tcg caa acc caa gaa tgt tgc acg ttt tat336 Ser Met Phe Asn Gln Ser Ser Gln Thr Gln Glu Cys Cys Thr Phe Tyr 95100 105 110 tgc caa tcc tgc ggt gaa gtc ata ata aaa gac agg aag ctc ctcagg 384 Cys Gln Ser Cys Gly Glu Val Ile Ile Lys Asp Arg Lys Leu Leu Arg115 120 125 gtg ctc cca ctg ccg agt gag aac tgg gga gct cta gtt gga gaatgg 432 Val Leu Pro Leu Pro Ser Glu Asn Trp Gly Ala Leu Val Gly Glu Trp130 135 140 tgt tgt cat cct gac ccc ttt gct aat aaa tca ctt cat ccg caagag 480 Cys Cys His Pro Asp Pro Phe Ala Asn Lys Ser Leu His Pro Gln Glu145 150 155 aat gac tgt ttt att gga gac tct ttc ttc ttg gtg aat tta agaacc 528 Asn Asp Cys Phe Ile Gly Asp Ser Phe Phe Leu Val Asn Leu Arg Thr160 165 170 agt ttg tgg cag caa aga cct gaa cta tcc cca gtg gag atg tgctgt 576 Ser Leu Trp Gln Gln Arg Pro Glu Leu Ser Pro Val Glu Met Cys Cys175 180 185 190 gtt tct tct gac aac cat tgt aaa ttg gaa cca aag gca aatacc aaa 624 Val Ser Ser Asp Asn His Cys Lys Leu Glu Pro Lys Ala Asn ThrLys 195 200 205 gta att tgt aag cgt tgc aag gta atg ttg gga gag acc gtgtca tca 672 Val Ile Cys Lys Arg Cys Lys Val Met Leu Gly Glu Thr Val SerSer 210 215 220 gaa acc acc aag ttt tat atg aca gag ata att att cag tcatct gag 720 Glu Thr Thr Lys Phe Tyr Met Thr Glu Ile Ile Ile Gln Ser SerGlu 225 230 235 agg agt ttt cct atc ata cca agg tct tgg ttt gtc cag agcgtg atc 768 Arg Ser Phe Pro Ile Ile Pro Arg Ser Trp Phe Val Gln Ser ValIle 240 245 250 gcc cag tgt ctg gtg cag ctc tcc tct gct aga agc act tttaga ttc 816 Ala Gln Cys Leu Val Gln Leu Ser Ser Ala Arg Ser Thr Phe ArgPhe 255 260 265 270 acg att caa ggt cag gat gac aaa gtg tat atc ttg ctatgg ctt tta 864 Thr Ile Gln Gly Gln Asp Asp Lys Val Tyr Ile Leu Leu TrpLeu Leu 275 280 285 aat tca gac agt ttg gtg att gaa tct ttg aga aat tccaaa tat atc 912 Asn Ser Asp Ser Leu Val Ile Glu Ser Leu Arg Asn Ser LysTyr Ile 290 295 300 aaa aaa ttc ccc ttg ttg gaa aac aca ttc aaa gcc gattct agt tct 960 Lys Lys Phe Pro Leu Leu Glu Asn Thr Phe Lys Ala Asp SerSer Ser 305 310 315 gcc tgg agt gct gtc aag gtc ctc tac cag cca tgc atcaaa agc agg 1008 Ala Trp Ser Ala Val Lys Val Leu Tyr Gln Pro Cys Ile LysSer Arg 320 325 330 aat gaa aaa ctt gtc agc ttg tgg gaa agt gac atc agcgtc cac ccg 1056 Asn Glu Lys Leu Val Ser Leu Trp Glu Ser Asp Ile Ser ValHis Pro 335 340 345 350 cta acc ctg ccc tct gca acc tgc ttg gag ctg ctgttg ata ttg tca 1104 Leu Thr Leu Pro Ser Ala Thr Cys Leu Glu Leu Leu LeuIle Leu Ser 355 360 365 aag agt aat gcc aat ctg cct tca tcc ctt cgc cgtgtg aat tcc ttt 1152 Lys Ser Asn Ala Asn Leu Pro Ser Ser Leu Arg Arg ValAsn Ser Phe 370 375 380 cag gtg agc aat ggc ttc ttt tct agg ccgtgatttctc 1191 Gln Val Ser Asn Gly Phe Phe Ser Arg Pro 385 390 48 392PRT Homo sapiens 48 Met Ala Ala Ser Ala Ala Glu Thr Arg Val Phe Leu GluVal Arg Gly 1 5 10 15 Gln Leu Gln Ser Ala Leu Leu Ile Leu Gly Glu ProLys Glu Gly Gly 20 25 30 Met Pro Met Asn Ile Ser Ile Met Pro Ser Ser LeuGln Met Lys Thr 35 40 45 Pro Glu Gly Cys Thr Glu Ile Gln Leu Pro Ala GluVal Arg Leu Val 50 55 60 Pro Ser Ser Cys Arg Gly Leu Gln Phe Val Val GlyAsp Gly Leu His 65 70 75 80 Leu Arg Leu Gln Thr Gln Ala Lys Leu Gly ThrLys Leu Ile Ser Met 85 90 95 Phe Asn Gln Ser Ser Gln Thr Gln Glu Cys CysThr Phe Tyr Cys Gln 100 105 110 Ser Cys Gly Glu Val Ile Ile Lys Asp ArgLys Leu Leu Arg Val Leu 115 120 125 Pro Leu Pro Ser Glu Asn Trp Gly AlaLeu Val Gly Glu Trp Cys Cys 130 135 140 His Pro Asp Pro Phe Ala Asn LysSer Leu His Pro Gln Glu Asn Asp 145 150 155 160 Cys Phe Ile Gly Asp SerPhe Phe Leu Val Asn Leu Arg Thr Ser Leu 165 170 175 Trp Gln Gln Arg ProGlu Leu Ser Pro Val Glu Met Cys Cys Val Ser 180 185 190 Ser Asp Asn HisCys Lys Leu Glu Pro Lys Ala Asn Thr Lys Val Ile 195 200 205 Cys Lys ArgCys Lys Val Met Leu Gly Glu Thr Val Ser Ser Glu Thr 210 215 220 Thr LysPhe Tyr Met Thr Glu Ile Ile Ile Gln Ser Ser Glu Arg Ser 225 230 235 240Phe Pro Ile Ile Pro Arg Ser Trp Phe Val Gln Ser Val Ile Ala Gln 245 250255 Cys Leu Val Gln Leu Ser Ser Ala Arg Ser Thr Phe Arg Phe Thr Ile 260265 270 Gln Gly Gln Asp Asp Lys Val Tyr Ile Leu Leu Trp Leu Leu Asn Ser275 280 285 Asp Ser Leu Val Ile Glu Ser Leu Arg Asn Ser Lys Tyr Ile LysLys 290 295 300 Phe Pro Leu Leu Glu Asn Thr Phe Lys Ala Asp Ser Ser SerAla Trp 305 310 315 320 Ser Ala Val Lys Val Leu Tyr Gln Pro Cys Ile LysSer Arg Asn Glu 325 330 335 Lys Leu Val Ser Leu Trp Glu Ser Asp Ile SerVal His Pro Leu Thr 340 345 350 Leu Pro Ser Ala Thr Cys Leu Glu Leu LeuLeu Ile Leu Ser Lys Ser 355 360 365 Asn Ala Asn Leu Pro Ser Ser Leu ArgArg Val Asn Ser Phe Gln Val 370 375 380 Ser Asn Gly Phe Phe Ser Arg Pro385 390 49 8848 DNA Homo sapiens CDS (61)..(8484) 49 tataacggtaccggcggcgg cagcgccgct gctcttccct tctcctcagg aggggggcca 60 atg gct agcgag aag ccg ggc ccg ggc ccg ggg ctc gag cct cag ccc 108 Met Ala Ser GluLys Pro Gly Pro Gly Pro Gly Leu Glu Pro Gln Pro 1 5 10 15 gtg ggg ctcatt gcc gtc ggg gcc gct ggc gga ggc ggc ggg ggc agc 156 Val Gly Leu IleAla Val Gly Ala Ala Gly Gly Gly Gly Gly Gly Ser 20 25 30 ggt ggt ggc ggcacc ggg ggc agc ggg atg ggg gag cta agg ggg gcg 204 Gly Gly Gly Gly ThrGly Gly Ser Gly Met Gly Glu Leu Arg Gly Ala 35 40 45 tcc ggc tcc ggc tcggtg atg ctc ccc gcg ggg atg att aac cct tcg 252 Ser Gly Ser Gly Ser ValMet Leu Pro Ala Gly Met Ile Asn Pro Ser 50 55 60 gtg ccg atc cgc aac atccgg atg aaa ttc gca gtg ttg att gga ctc 300 Val Pro Ile Arg Asn Ile ArgMet Lys Phe Ala Val Leu Ile Gly Leu 65 70 75 80 ata cag gtc gga gag gtcagc aac agg gac atc gtg gag acg gtg ctc 348 Ile Gln Val Gly Glu Val SerAsn Arg Asp Ile Val Glu Thr Val Leu 85 90 95 aac ctg ctg gtt ggt gga gaattt gac ttg gag atg aac ttt att atc 396 Asn Leu Leu Val Gly Gly Glu PheAsp Leu Glu Met Asn Phe Ile Ile 100 105 110 cag gat gct gag agt ata acatgt atg aca gag ctt ttg gag cac tgt 444 Gln Asp Ala Glu Ser Ile Thr CysMet Thr Glu Leu Leu Glu His Cys 115 120 125 gat gta aca tgt caa gca gaaata tgg agc atg ttt aca gcc att cta 492 Asp Val Thr Cys Gln Ala Glu IleTrp Ser Met Phe Thr Ala Ile Leu 130 135 140 cga aaa agt gtt cgg aat ttacag act agc aca gaa gtt ggg cta att 540 Arg Lys Ser Val Arg Asn Leu GlnThr Ser Thr Glu Val Gly Leu Ile 145 150 155 160 gaa caa gta ttg ctg aaaatg agt gct gta gat gac atg ata gca gat 588 Glu Gln Val Leu Leu Lys MetSer Ala Val Asp Asp Met Ile Ala Asp 165 170 175 ctt cta gtt gat atg ttgggg gtt ctt gcc agc tac agc atc act gtc 636 Leu Leu Val Asp Met Leu GlyVal Leu Ala Ser Tyr Ser Ile Thr Val 180 185 190 aag gag ttg aag ctt ttgttc agc atg ctt cga gga gaa agt gga atc 684 Lys Glu Leu Lys Leu Leu PheSer Met Leu Arg Gly Glu Ser Gly Ile 195 200 205 tgg cca aga cat gca gtaaaa tta tta tca gtt ctt aat cag atg cca 732 Trp Pro Arg His Ala Val LysLeu Leu Ser Val Leu Asn Gln Met Pro 210 215 220 cag aga cac ggt cct gatact ttt ttc aat ttc cct ggt tgt agc gct 780 Gln Arg His Gly Pro Asp ThrPhe Phe Asn Phe Pro Gly Cys Ser Ala 225 230 235 240 gcg gca att gcc ttgcct cct att gca aag tgg cct tat cag aat ggc 828 Ala Ala Ile Ala Leu ProPro Ile Ala Lys Trp Pro Tyr Gln Asn Gly 245 250 255 ttc acc tta aac acttgg ttt cgt atg gat cca tta aat aat att aat 876 Phe Thr Leu Asn Thr TrpPhe Arg Met Asp Pro Leu Asn Asn Ile Asn 260 265 270 gtt gat aag gat aaacct tat ctt tat tgt ttt cgt act agc aaa gga 924 Val Asp Lys Asp Lys ProTyr Leu Tyr Cys Phe Arg Thr Ser Lys Gly 275 280 285 gtt ggt tac tct gctcat ttt gtt ggc aac tgt tta ata gtc aca tca 972 Val Gly Tyr Ser Ala HisPhe Val Gly Asn Cys Leu Ile Val Thr Ser 290 295 300 ttg aag tcc aaa ggaaaa ggt ttt cag cat tgt gtg aaa tat gat ttt 1020 Leu Lys Ser Lys Gly LysGly Phe Gln His Cys Val Lys Tyr Asp Phe 305 310 315 320 caa cca cgc aagtgg tac atg atc agc att gtc cac att tac aat cga 1068 Gln Pro Arg Lys TrpTyr Met Ile Ser Ile Val His Ile Tyr Asn Arg 325 330 335 tgg agg aac agtgaa att cgg tgt tat gtt aat gga caa ctg gta tct 1116 Trp Arg Asn Ser GluIle Arg Cys Tyr Val Asn Gly Gln Leu Val Ser 340 345 350 tat ggt gat atggct tgg cat gtt aac aca aat gat agc tat gac aag 1164 Tyr Gly Asp Met AlaTrp His Val Asn Thr Asn Asp Ser Tyr Asp Lys 355 360 365 tgc ttt ctt ggatca tca gaa act gct gat gca aat agg gta ttc tgt 1212 Cys Phe Leu Gly SerSer Glu Thr Ala Asp Ala Asn Arg Val Phe Cys 370 375 380 ggt caa ctt ggtgcc gtg tat gtg ttc agt gaa gca ctc aac cca gca 1260 Gly Gln Leu Gly AlaVal Tyr Val Phe Ser Glu Ala Leu Asn Pro Ala 385 390 395 400 cag ata tttgca att cat cag tta gga cct gga tat aag agt acc ttc 1308 Gln Ile Phe AlaIle His Gln Leu Gly Pro Gly Tyr Lys Ser Thr Phe 405 410 415 aag ttt aaatct gag agt gat att cat ttg gca gaa cat cat aaa cag 1356 Lys Phe Lys SerGlu Ser Asp Ile His Leu Ala Glu His His Lys Gln 420 425 430 gtg tta tatgat ggg aaa ctt gca agt agc att gcc ttt aca tat aat 1404 Val Leu Tyr AspGly Lys Leu Ala Ser Ser Ile Ala Phe Thr Tyr Asn 435 440 445 gct aag gccact gat gct cag ctc tgc ctg gaa tca tca cca aaa gag 1452 Ala Lys Ala ThrAsp Ala Gln Leu Cys Leu Glu Ser Ser Pro Lys Glu 450 455 460 aat gca tcaatt ttt gtg cat tcc cca cat gct cta atg ctt cag gat 1500 Asn Ala Ser IlePhe Val His Ser Pro His Ala Leu Met Leu Gln Asp 465 470 475 480 gtg aaagcg ata gta aca cat tca att cat agt gca att cat tca att 1548 Val Lys AlaIle Val Thr His Ser Ile His Ser Ala Ile His Ser Ile 485 490 495 gga gggatt caa gtg ctt ttt cca ctt ttt gcc caa ttg gat aat agg 1596 Gly Gly IleGln Val Leu Phe Pro Leu Phe Ala Gln Leu Asp Asn Arg 500 505 510 cag ctcaat gac agt caa gtg gaa aca act gtt gct act ctg ttg gca 1644 Gln Leu AsnAsp Ser Gln Val Glu Thr Thr Val Ala Thr Leu Leu Ala 515 520 525 ttc ctggtt gaa cta ctt aaa agt tca gta gcc atg caa gaa cag atg 1692 Phe Leu ValGlu Leu Leu Lys Ser Ser Val Ala Met Gln Glu Gln Met 530 535 540 ctg ggtgga aaa ggc ttt tta gtc att ggc tac tta ctt gaa aag tca 1740 Leu Gly GlyLys Gly Phe Leu Val Ile Gly Tyr Leu Leu Glu Lys Ser 545 550 555 560 tcaaga gtt cat ata act aga gct gtc ctg gag caa ttt tta tct ttt 1788 Ser ArgVal His Ile Thr Arg Ala Val Leu Glu Gln Phe Leu Ser Phe 565 570 575 gcaaaa tac ctt gat ggt tta tct cat gga gca cct ttg ctg aag cag 1836 Ala LysTyr Leu Asp Gly Leu Ser His Gly Ala Pro Leu Leu Lys Gln 580 585 590 ctttgt gat cac att tta ttt aac cca gcc atc tgg ata cat aca cct 1884 Leu CysAsp His Ile Leu Phe Asn Pro Ala Ile Trp Ile His Thr Pro 595 600 605 gcaaag gtt cag ctt tcc cta tac aca tat ttg tct gct gaa ttt att 1932 Ala LysVal Gln Leu Ser Leu Tyr Thr Tyr Leu Ser Ala Glu Phe Ile 610 615 620 ggaact gct acc atc tac acc acc ata cgc aga gta gga aca gta tta 1980 Gly ThrAla Thr Ile Tyr Thr Thr Ile Arg Arg Val Gly Thr Val Leu 625 630 635 640cag cta atg cac acc tta aaa tat tac tac tgg gtt att aat cct gct 2028 GlnLeu Met His Thr Leu Lys Tyr Tyr Tyr Trp Val Ile Asn Pro Ala 645 650 655gac agt agt ggc att aca cct aaa gga tta gat ggt ccc cgg cca tca 2076 AspSer Ser Gly Ile Thr Pro Lys Gly Leu Asp Gly Pro Arg Pro Ser 660 665 670caa aaa gaa att ata tca ctg agg gca ttt atg cta ctt ttt ctg aaa 2124 GlnLys Glu Ile Ile Ser Leu Arg Ala Phe Met Leu Leu Phe Leu Lys 675 680 685cag ctg ata cta aag gat cga ggg gtc aag gaa gat gaa ctt cag agt 2172 GlnLeu Ile Leu Lys Asp Arg Gly Val Lys Glu Asp Glu Leu Gln Ser 690 695 700ata tta aat tac cta ctt acg atg cat gag gat gaa aat att cat gat 2220 IleLeu Asn Tyr Leu Leu Thr Met His Glu Asp Glu Asn Ile His Asp 705 710 715720 gtg cta cag tta ctg gtg gct tta atg tcg gaa cac cca gcc tca atg 2268Val Leu Gln Leu Leu Val Ala Leu Met Ser Glu His Pro Ala Ser Met 725 730735 ata cca gca ttt gat caa aga aat gga ata agg gtg atc tac aaa tta 2316Ile Pro Ala Phe Asp Gln Arg Asn Gly Ile Arg Val Ile Tyr Lys Leu 740 745750 ttg gct tct aaa agt gaa agt att tgg gtt caa gct ttg aag gtt ctg 2364Leu Ala Ser Lys Ser Glu Ser Ile Trp Val Gln Ala Leu Lys Val Leu 755 760765 gga tac ttt ctg aag cat tta ggt cac aag aga aaa gtt gaa att atg 2412Gly Tyr Phe Leu Lys His Leu Gly His Lys Arg Lys Val Glu Ile Met 770 775780 cac acc cat agt ctt ttc act ctt ctt gga gaa agg ctg atg ttg cat 2460His Thr His Ser Leu Phe Thr Leu Leu Gly Glu Arg Leu Met Leu His 785 790795 800 aca aac act gtg act gtc acc aca tac aac aca ctt tat gag atc ttg2508 Thr Asn Thr Val Thr Val Thr Thr Tyr Asn Thr Leu Tyr Glu Ile Leu 805810 815 aca gaa caa gta tgt act cag gtc gta cac aaa cca cat cca gag cca2556 Thr Glu Gln Val Cys Thr Gln Val Val His Lys Pro His Pro Glu Pro 820825 830 gat tct aca gtg aaa att cag aat cca atg att ctt aaa gtg gtg gca2604 Asp Ser Thr Val Lys Ile Gln Asn Pro Met Ile Leu Lys Val Val Ala 835840 845 act ttg tta aaa aac tct aca cca agt gca gag ctg atg gaa gtt cgt2652 Thr Leu Leu Lys Asn Ser Thr Pro Ser Ala Glu Leu Met Glu Val Arg 850855 860 cgt tta ttt tta tct gat atg ata aaa ctt ttc agt aac agc cgt gaa2700 Arg Leu Phe Leu Ser Asp Met Ile Lys Leu Phe Ser Asn Ser Arg Glu 865870 875 880 aat aga aga tgc tta ttg cag tgt tca gtg tgg cag gat tgg atgttt 2748 Asn Arg Arg Cys Leu Leu Gln Cys Ser Val Trp Gln Asp Trp Met Phe885 890 895 tct ctt ggc tat atc aat cct aaa aat tct gag gaa cag aag attacc 2796 Ser Leu Gly Tyr Ile Asn Pro Lys Asn Ser Glu Glu Gln Lys Ile Thr900 905 910 gaa atg gtc tac aat atc ttc cgg att ctt ttg tat cat gca ataaaa 2844 Glu Met Val Tyr Asn Ile Phe Arg Ile Leu Leu Tyr His Ala Ile Lys915 920 925 tat gaa tgg gga ggc tgg aga gtc tgg gtg gat acc ctc tca atagcc 2892 Tyr Glu Trp Gly Gly Trp Arg Val Trp Val Asp Thr Leu Ser Ile Ala930 935 940 cat tcc aag gtc act tat gaa gct cat aag gaa tac cta gcc aaaatg 2940 His Ser Lys Val Thr Tyr Glu Ala His Lys Glu Tyr Leu Ala Lys Met945 950 955 960 tat gag gaa tat caa aga caa gag gag gaa aac att aaa aaggga aag 2988 Tyr Glu Glu Tyr Gln Arg Gln Glu Glu Glu Asn Ile Lys Lys GlyLys 965 970 975 aaa ggg aat gtg agc acc atc tct ggt ctt tca tca cag acaaca gga 3036 Lys Gly Asn Val Ser Thr Ile Ser Gly Leu Ser Ser Gln Thr ThrGly 980 985 990 gca aaa ggt gga atg gaa att cga gag ata gaa gat ctt tcacaa agc 3084 Ala Lys Gly Gly Met Glu Ile Arg Glu Ile Glu Asp Leu Ser GlnSer 995 1000 1005 cag agc cca gaa agt gag acc gat tac cct gtc agc acagat act cga 3132 Gln Ser Pro Glu Ser Glu Thr Asp Tyr Pro Val Ser Thr AspThr Arg 1010 1015 1020 gac tta ctc atg tca aca aaa gtg tca gat gat attctt gga aat tca 3180 Asp Leu Leu Met Ser Thr Lys Val Ser Asp Asp Ile LeuGly Asn Ser 1025 1030 1035 1040 gat aga cca gga agt ggt gta cat gtg gaagta cat gat ctt tta gta 3228 Asp Arg Pro Gly Ser Gly Val His Val Glu ValHis Asp Leu Leu Val 1045 1050 1055 gat ata aaa gca gag aaa gtg gaa gcaaca gaa gta aag ctc gat gat 3276 Asp Ile Lys Ala Glu Lys Val Glu Ala ThrGlu Val Lys Leu Asp Asp 1060 1065 1070 atg gat tta tca ccg gag act ttagta ggt gga gag aat ggt gcc ctt 3324 Met Asp Leu Ser Pro Glu Thr Leu ValGly Gly Glu Asn Gly Ala Leu 1075 1080 1085 gtg gag gtt gaa tct ctg ttggat aat gta tat agt gct gct gtt gag 3372 Val Glu Val Glu Ser Leu Leu AspAsn Val Tyr Ser Ala Ala Val Glu 1090 1095 1100 aaa ctc cag aac aat gtacat gga agt gtt ggt atc att aaa aaa aat 3420 Lys Leu Gln Asn Asn Val HisGly Ser Val Gly Ile Ile Lys Lys Asn 1105 1110 1115 1120 gaa gaa aag gataat ggt cca ttg ata aca tta gca gat gag aaa gaa 3468 Glu Glu Lys Asp AsnGly Pro Leu Ile Thr Leu Ala Asp Glu Lys Glu 1125 1130 1135 gac ctt cccaat agt agt aca tca ttt ctc ttt gat aaa ata ccc aaa 3516 Asp Leu Pro AsnSer Ser Thr Ser Phe Leu Phe Asp Lys Ile Pro Lys 1140 1145 1150 cag gaggaa aaa cta ctt cct gaa ctt tct agc aat cac att att cca 3564 Gln Glu GluLys Leu Leu Pro Glu Leu Ser Ser Asn His Ile Ile Pro 1155 1160 1165 aatatt cag gac aca caa gta cat ctt ggt gtt agt gat gat ctt gga 3612 Asn IleGln Asp Thr Gln Val His Leu Gly Val Ser Asp Asp Leu Gly 1170 1175 1180ttg ctt gct cac atg acc ggt agc gta gac tta act tgt aca tcc agt 3660 LeuLeu Ala His Met Thr Gly Ser Val Asp Leu Thr Cys Thr Ser Ser 1185 11901195 1200 ata ata gaa gaa aaa gaa ttc aaa atc cat aca act tca gat ggaatg 3708 Ile Ile Glu Glu Lys Glu Phe Lys Ile His Thr Thr Ser Asp Gly Met1205 1210 1215 agc agt att tct gaa aga gac tta gcg tca tca act aag gggctg gag 3756 Ser Ser Ile Ser Glu Arg Asp Leu Ala Ser Ser Thr Lys Gly LeuGlu 1220 1225 1230 tat gct gaa atg act gct aca act ctg gaa act gag tcttct agt agc 3804 Tyr Ala Glu Met Thr Ala Thr Thr Leu Glu Thr Glu Ser SerSer Ser 1235 1240 1245 aaa att gta cca aat att gat gca gga agt ata atttca gat act gaa 3852 Lys Ile Val Pro Asn Ile Asp Ala Gly Ser Ile Ile SerAsp Thr Glu 1250 1255 1260 agg tct gac gat ggc aaa gaa tca gga aaa gaaatc cga aaa atc caa 3900 Arg Ser Asp Asp Gly Lys Glu Ser Gly Lys Glu IleArg Lys Ile Gln 1265 1270 1275 1280 aca act act acg aca caa ggt cgg tctatc acc caa caa gac cga gat 3948 Thr Thr Thr Thr Thr Gln Gly Arg Ser IleThr Gln Gln Asp Arg Asp 1285 1290 1295 ctc cga gtt gat tta gga ttt cgagga atg cca atg act gag gaa cag 3996 Leu Arg Val Asp Leu Gly Phe Arg GlyMet Pro Met Thr Glu Glu Gln 1300 1305 1310 cga cgc cag ttt agc cca ggtcca cgg act aca atg ttt cgt att cct 4044 Arg Arg Gln Phe Ser Pro Gly ProArg Thr Thr Met Phe Arg Ile Pro 1315 1320 1325 gag ttt aaa tgg tct ccaatg cac cag cgg ctt ctc act gat tta cta 4092 Glu Phe Lys Trp Ser Pro MetHis Gln Arg Leu Leu Thr Asp Leu Leu 1330 1335 1340 ttt gca tta gaa actgat gta cat gtt tgg agg agc cat tct aca aag 4140 Phe Ala Leu Glu Thr AspVal His Val Trp Arg Ser His Ser Thr Lys 1345 1350 1355 1360 tct gta atggat ttt gtc aat agc aat gaa aat att att ttt gta cat 4188 Ser Val Met AspPhe Val Asn Ser Asn Glu Asn Ile Ile Phe Val His 1365 1370 1375 aac acaatt cac ctc att tcc caa atg gta gac aac atc atc att gct 4236 Asn Thr IleHis Leu Ile Ser Gln Met Val Asp Asn Ile Ile Ile Ala 1380 1385 1390 tgtgga gga att tta cct ttg ctc tct gct gct aca tca cca act ggt 4284 Cys GlyGly Ile Leu Pro Leu Leu Ser Ala Ala Thr Ser Pro Thr Gly 1395 1400 1405tct aag acg gaa ttg gaa aat att gaa gtg aca caa ggc atg tca gct 4332 SerLys Thr Glu Leu Glu Asn Ile Glu Val Thr Gln Gly Met Ser Ala 1410 14151420 gag aca gca gta act ttc ctc agc cgg ctg atg gct atg gtt gat gta4380 Glu Thr Ala Val Thr Phe Leu Ser Arg Leu Met Ala Met Val Asp Val1425 1430 1435 1440 ctt gtg ttt gca agc tct cta aat ttt agt gag att gaagct gag aaa 4428 Leu Val Phe Ala Ser Ser Leu Asn Phe Ser Glu Ile Glu AlaGlu Lys 1445 1450 1455 aac atg tct tct gga ggt tta atg cga cag tgc ctaaga tta gtt tgt 4476 Asn Met Ser Ser Gly Gly Leu Met Arg Gln Cys Leu ArgLeu Val Cys 1460 1465 1470 tgt gtt gct gtg aga aac tgt tta gaa tgt cggcaa aga cag aga gac 4524 Cys Val Ala Val Arg Asn Cys Leu Glu Cys Arg GlnArg Gln Arg Asp 1475 1480 1485 agg gga aat aaa tct tcc cat gga agc agtaaa cct cag gaa gtt cct 4572 Arg Gly Asn Lys Ser Ser His Gly Ser Ser LysPro Gln Glu Val Pro 1490 1495 1500 caa agt act cca ttg gaa aat gtt ccaggt aac ctt tct cct att aag 4620 Gln Ser Thr Pro Leu Glu Asn Val Pro GlyAsn Leu Ser Pro Ile Lys 1505 1510 1515 1520 gat ccg gat aga ctt ctt caggat gtt gat atc aat cgc ctt cgt gct 4668 Asp Pro Asp Arg Leu Leu Gln AspVal Asp Ile Asn Arg Leu Arg Ala 1525 1530 1535 gtt gtc ttt cgg gat gtggat gat agc aaa caa gca cag ttc tta gct 4716 Val Val Phe Arg Asp Val AspAsp Ser Lys Gln Ala Gln Phe Leu Ala 1540 1545 1550 ctg gct gtt gtt tacttc att tcg gtt ctg atg gtt tcc aag tat cgt 4764 Leu Ala Val Val Tyr PheIle Ser Val Leu Met Val Ser Lys Tyr Arg 1555 1560 1565 gac ata tta gaaccc cag aga gag act aca aga act gga agc caa cca 4812 Asp Ile Leu Glu ProGln Arg Glu Thr Thr Arg Thr Gly Ser Gln Pro 1570 1575 1580 ggt aga aacatc agg caa gaa ata aat tca cca aca agt aca gaa aca 4860 Gly Arg Asn IleArg Gln Glu Ile Asn Ser Pro Thr Ser Thr Glu Thr 1585 1590 1595 1600 cctgct gca ttt cca gac acc ata aaa gaa aaa gaa aca cca act cct 4908 Pro AlaAla Phe Pro Asp Thr Ile Lys Glu Lys Glu Thr Pro Thr Pro 1605 1610 1615ggt gaa gat att cag gta gaa agt tca att ccc cat aca gat tca gga 4956 GlyGlu Asp Ile Gln Val Glu Ser Ser Ile Pro His Thr Asp Ser Gly 1620 16251630 att gga gag gag caa gtg gct agc atc ctg aat ggg gca gaa tta gaa5004 Ile Gly Glu Glu Gln Val Ala Ser Ile Leu Asn Gly Ala Glu Leu Glu1635 1640 1645 aca agt aca ggc cct gat gcc atg agt gaa ctc tta tcc actttg tca 5052 Thr Ser Thr Gly Pro Asp Ala Met Ser Glu Leu Leu Ser Thr LeuSer 1650 1655 1660 tcc gaa gtg aag aaa tca caa gag agc tta act gaa aatcct agt gaa 5100 Ser Glu Val Lys Lys Ser Gln Glu Ser Leu Thr Glu Asn ProSer Glu 1665 1670 1675 1680 acg ttg aag cct gca aca tcc ata tct agc attagt caa acc aaa ggc 5148 Thr Leu Lys Pro Ala Thr Ser Ile Ser Ser Ile SerGln Thr Lys Gly 1685 1690 1695 atc aat gtg aag gaa ata ctg aaa agt cttgtg gct gct cca gtt gaa 5196 Ile Asn Val Lys Glu Ile Leu Lys Ser Leu ValAla Ala Pro Val Glu 1700 1705 1710 ata gca gaa tgt ggc cct gaa cct atccca tac cca gat cca gca ttg 5244 Ile Ala Glu Cys Gly Pro Glu Pro Ile ProTyr Pro Asp Pro Ala Leu 1715 1720 1725 aag aga gaa aca caa gct att cttcct atg cag ttt cat tcc ttt gac 5292 Lys Arg Glu Thr Gln Ala Ile Leu ProMet Gln Phe His Ser Phe Asp 1730 1735 1740 agc atc act gca aaa ctt gaaaga gcg tta gaa aaa gtt gct cct ctt 5340 Ser Ile Thr Ala Lys Leu Glu ArgAla Leu Glu Lys Val Ala Pro Leu 1745 1750 1755 1760 ctt cgt gaa att tttgta gac ttt gcc cca ttc cta tct cgt aca ctt 5388 Leu Arg Glu Ile Phe ValAsp Phe Ala Pro Phe Leu Ser Arg Thr Leu 1765 1770 1775 ctt ggc agt catgga caa gag cta ttg ata gaa ggc ctt gtt tgt atg 5436 Leu Gly Ser His GlyGln Glu Leu Leu Ile Glu Gly Leu Val Cys Met 1780 1785 1790 aag tcc agcaca tct gtg gtt gag ctt gtt atg ctg ctt tgt tct cag 5484 Lys Ser Ser ThrSer Val Val Glu Leu Val Met Leu Leu Cys Ser Gln 1795 1800 1805 gaa tggcaa aac tct att cag aag aat gca gga ctt gca ttt att gag 5532 Glu Trp GlnAsn Ser Ile Gln Lys Asn Ala Gly Leu Ala Phe Ile Glu 1810 1815 1820 ctcatc aat gaa gga aga tta ctg tgc cat gct atg aag gac cat ata 5580 Leu IleAsn Glu Gly Arg Leu Leu Cys His Ala Met Lys Asp His Ile 1825 1830 18351840 gtc cgt gtt gca aat gaa gct gag ttt att ttg aac aga caa aga gcc5628 Val Arg Val Ala Asn Glu Ala Glu Phe Ile Leu Asn Arg Gln Arg Ala1845 1850 1855 gag gat gta cat aaa cat gca gag ttt gag tca cag tgt gcccaa tat 5676 Glu Asp Val His Lys His Ala Glu Phe Glu Ser Gln Cys Ala GlnTyr 1860 1865 1870 gct gct gat aga aga gag gaa gaa aag atg tgt gac catctt atc agt 5724 Ala Ala Asp Arg Arg Glu Glu Glu Lys Met Cys Asp His LeuIle Ser 1875 1880 1885 gct gct aaa cat cga gat cat gta aca gca aat cagctg aaa cag aag 5772 Ala Ala Lys His Arg Asp His Val Thr Ala Asn Gln LeuLys Gln Lys 1890 1895 1900 att ctc aat att ctc aca aat aaa cat ggt gcttgg gga gca gtt tct 5820 Ile Leu Asn Ile Leu Thr Asn Lys His Gly Ala TrpGly Ala Val Ser 1905 1910 1915 1920 cat agc caa ttg cat gat ttc tgg cgtttg gat tac tgg gaa gat gat 5868 His Ser Gln Leu His Asp Phe Trp Arg LeuAsp Tyr Trp Glu Asp Asp 1925 1930 1935 ctt cgt cga agg aga cga ttt gttcgc aat gca ttt ggc tcc act cat 5916 Leu Arg Arg Arg Arg Arg Phe Val ArgAsn Ala Phe Gly Ser Thr His 1940 1945 1950 gct gaa gca ttg ctg aaa gctgca ata gaa tat ggc acg gaa gaa gat 5964 Ala Glu Ala Leu Leu Lys Ala AlaIle Glu Tyr Gly Thr Glu Glu Asp 1955 1960 1965 gta gta aag tca aag aaaaca ttc aga agt caa gca ata gtg aac caa 6012 Val Val Lys Ser Lys Lys ThrPhe Arg Ser Gln Ala Ile Val Asn Gln 1970 1975 1980 aat gca gag aca gaactt atg ctg gaa gga gac gat gat gca gtc agt 6060 Asn Ala Glu Thr Glu LeuMet Leu Glu Gly Asp Asp Asp Ala Val Ser 1985 1990 1995 2000 ctg cta caggag aaa gaa att gac aac ctt gca ggc cca gtg gtt ctc 6108 Leu Leu Gln GluLys Glu Ile Asp Asn Leu Ala Gly Pro Val Val Leu 2005 2010 2015 agc acccct gcc cag ctc atc gct ccc gtg gtg gtg gcc aag ggg act 6156 Ser Thr ProAla Gln Leu Ile Ala Pro Val Val Val Ala Lys Gly Thr 2020 2025 2030 ctctcc atc acc acg aca gaa atc tac ttc gag gta gat gag gat gat 6204 Leu SerIle Thr Thr Thr Glu Ile Tyr Phe Glu Val Asp Glu Asp Asp 2035 2040 2045tct gcc ttc aag aag atc gac acg aaa gtt ctt gca tac act gag gga 6252 SerAla Phe Lys Lys Ile Asp Thr Lys Val Leu Ala Tyr Thr Glu Gly 2050 20552060 ctt cac gga aaa tgg atg ttc agc gag ata cga gct gta ttt tca aga6300 Leu His Gly Lys Trp Met Phe Ser Glu Ile Arg Ala Val Phe Ser Arg2065 2070 2075 2080 cgt tac ctt cta caa aac act gct ttg gaa gta ttt atggca aac cga 6348 Arg Tyr Leu Leu Gln Asn Thr Ala Leu Glu Val Phe Met AlaAsn Arg 2085 2090 2095 acc tca gtt atg ttt aat ttc cct gat caa gca acagta aaa aaa gtt 6396 Thr Ser Val Met Phe Asn Phe Pro Asp Gln Ala Thr ValLys Lys Val 2100 2105 2110 gtc tat agc ttg cct cgg gtt gga gta ggg accagc tat ggt ctg cca 6444 Val Tyr Ser Leu Pro Arg Val Gly Val Gly Thr SerTyr Gly Leu Pro 2115 2120 2125 caa gcc agg agg ata tca ttg gcc act cctcga cag ctt tat aaa tct 6492 Gln Ala Arg Arg Ile Ser Leu Ala Thr Pro ArgGln Leu Tyr Lys Ser 2130 2135 2140 tcc aat atg act cag cgc tgg caa agaagg gaa att tca aac ttc gaa 6540 Ser Asn Met Thr Gln Arg Trp Gln Arg ArgGlu Ile Ser Asn Phe Glu 2145 2150 2155 2160 tat ttg atg ttc ctt aat actatt gca gga cgg aca tat aat gat ctg 6588 Tyr Leu Met Phe Leu Asn Thr IleAla Gly Arg Thr Tyr Asn Asp Leu 2165 2170 2175 aac caa tat cca gtg tttccg tgg gtg tta acc aac tat gaa tca gaa 6636 Asn Gln Tyr Pro Val Phe ProTrp Val Leu Thr Asn Tyr Glu Ser Glu 2180 2185 2190 gag ttg gac ctg actctt cca gga aac ttc agg gat cta tca aag cca 6684 Glu Leu Asp Leu Thr LeuPro Gly Asn Phe Arg Asp Leu Ser Lys Pro 2195 2200 2205 att ggt gct ttgaac ccc aag aga gct gtg ttt tat gca gag cgt tat 6732 Ile Gly Ala Leu AsnPro Lys Arg Ala Val Phe Tyr Ala Glu Arg Tyr 2210 2215 2220 gag aca tgggaa gat gat caa agc cca ccc tac cat tat aat acc cat 6780 Glu Thr Trp GluAsp Asp Gln Ser Pro Pro Tyr His Tyr Asn Thr His 2225 2230 2235 2240 tattca aca gca aca tct act tta tcc tgg ctt gtt cga att gaa cct 6828 Tyr SerThr Ala Thr Ser Thr Leu Ser Trp Leu Val Arg Ile Glu Pro 2245 2250 2255ttc aca acc ttc ttc ctc aat gca aat gat gga aaa ttt gat cat cca 6876 PheThr Thr Phe Phe Leu Asn Ala Asn Asp Gly Lys Phe Asp His Pro 2260 22652270 gat cga acc ttc tca tcc gtt gca agg tct tgg aga act agt cag aga6924 Asp Arg Thr Phe Ser Ser Val Ala Arg Ser Trp Arg Thr Ser Gln Arg2275 2280 2285 gat act tct gat gta aag gaa cta att cca gag ttc tac taccta cca 6972 Asp Thr Ser Asp Val Lys Glu Leu Ile Pro Glu Phe Tyr Tyr LeuPro 2290 2295 2300 gag atg ttt gtc aac agt aat gga tat aat ctt gga gtcaga gaa gat 7020 Glu Met Phe Val Asn Ser Asn Gly Tyr Asn Leu Gly Val ArgGlu Asp 2305 2310 2315 2320 gaa gta gtg gta aat gat gtt gat ctt ccc ccttgg gca aaa aaa cct 7068 Glu Val Val Val Asn Asp Val Asp Leu Pro Pro TrpAla Lys Lys Pro 2325 2330 2335 gaa gac ttt gtg cgg atc aac agg atg gcccta gaa agt gaa ttt gtt 7116 Glu Asp Phe Val Arg Ile Asn Arg Met Ala LeuGlu Ser Glu Phe Val 2340 2345 2350 tct tgc caa ctt cat cag tgg atc gacctt ata ttt ggc tat aag cag 7164 Ser Cys Gln Leu His Gln Trp Ile Asp LeuIle Phe Gly Tyr Lys Gln 2355 2360 2365 cga gga cca gaa gca gtt cgt gctctg aat gtt ttt cac tac ttg act 7212 Arg Gly Pro Glu Ala Val Arg Ala LeuAsn Val Phe His Tyr Leu Thr 2370 2375 2380 tat gaa ggc tct gtg aac ctggat agt atc act gat cct gtg ctc agg 7260 Tyr Glu Gly Ser Val Asn Leu AspSer Ile Thr Asp Pro Val Leu Arg 2385 2390 2395 2400 gag gcc atg gag gcacag ata cag aac ttt gga cag acg cca tct cag 7308 Glu Ala Met Glu Ala GlnIle Gln Asn Phe Gly Gln Thr Pro Ser Gln 2405 2410 2415 ttg ctt att gagcca cat ccg cct cgg agc tct gcc atg cac ctg tgt 7356 Leu Leu Ile Glu ProHis Pro Pro Arg Ser Ser Ala Met His Leu Cys 2420 2425 2430 ttc ctt ccacag agt ccg ctc atg ttt aaa gat cag atg caa cag gat 7404 Phe Leu Pro GlnSer Pro Leu Met Phe Lys Asp Gln Met Gln Gln Asp 2435 2440 2445 gtg ataatg gtg ctg aag ttt cct tca aat tct cca gta acc cat gtg 7452 Val Ile MetVal Leu Lys Phe Pro Ser Asn Ser Pro Val Thr His Val 2450 2455 2460 gcagcc aac act ctg ccc cac ttg acc atc ccc gca gtg gtg aca gtg 7500 Ala AlaAsn Thr Leu Pro His Leu Thr Ile Pro Ala Val Val Thr Val 246 5 2470 24752480 act tgc agc cga ctc ttt gca gtg aat aga tgg cac aac aca gta ggc7548 Thr Cys Ser Arg Leu Phe Ala Val Asn Arg Trp His Asn Thr Val Gly2485 2490 2495 ctc aga gga gct cca gga tac tcc ttg gat caa gcc cac catctt ccc 7596 Leu Arg Gly Ala Pro Gly Tyr Ser Leu Asp Gln Ala His His LeuPro 2500 2505 2510 att gaa atg gat cca tta ata gcc aat aat tca ggt gtaaac aaa cgg 7644 Ile Glu Met Asp Pro Leu Ile Ala Asn Asn Ser Gly Val AsnLys Arg 2515 2520 2525 cag atc aca gac ctc gtt gac cag agt ata caa atcaat gca cat tgt 7692 Gln Ile Thr Asp Leu Val Asp Gln Ser Ile Gln Ile AsnAla His Cys 2530 2535 2540 ttt gtg gta aca gca gat aat cgc tat att cttatc tgt gga ttc tgg 7740 Phe Val Val Thr Ala Asp Asn Arg Tyr Ile Leu IleCys Gly Phe Trp 2545 2550 2555 2560 gat aag agc ttc aga gtt tat tct acagaa aca ggg aaa ttg act cag 7788 Asp Lys Ser Phe Arg Val Tyr Ser Thr GluThr Gly Lys Leu Thr Gln 2565 2570 2575 att gta ttt ggc cat tgg gat gtggtc act tgc ttg gcc agg tcc gag 7836 Ile Val Phe Gly His Trp Asp Val ValThr Cys Leu Ala Arg Ser Glu 2580 2585 2590 tca tac att ggt ggg gac tgctac atc gtg tcc gga tct cga gat gcc 7884 Ser Tyr Ile Gly Gly Asp Cys TyrIle Val Ser Gly Ser Arg Asp Ala 2595 2600 2605 acc ctg ctg ctc tgg tactgg agt ggg cgg cac cat atc ata gga gac 7932 Thr Leu Leu Leu Trp Tyr TrpSer Gly Arg His His Ile Ile Gly Asp 2610 2615 2620 aac cct aac agc agtgac tat ccg gca cca aga gcc gtc ctc aca ggc 7980 Asn Pro Asn Ser Ser AspTyr Pro Ala Pro Arg Ala Val Leu Thr Gly 2625 2630 2635 2640 cat gac catgaa gtt gtc tgt gtt tct gtc tgt gca gaa ctt ggg ctt 8028 His Asp His GluVal Val Cys Val Ser Val Cys Ala Glu Leu Gly Leu 2645 2650 2655 gtt atcagt ggt gct aaa gag ggc cct tgc ctt gtc cac acc atc act 8076 Val Ile SerGly Ala Lys Glu Gly Pro Cys Leu Val His Thr Ile Thr 2660 2665 2670 ggagat ttg ctg aga gcc ctt gaa gga cca gaa aac tgc tta ttc cca 8124 Gly AspLeu Leu Arg Ala Leu Glu Gly Pro Glu Asn Cys Leu Phe Pro 2675 2680 2685cgc ttg ata tct gtc tcc agc gaa ggc cac tgt atc ata tac tat gaa 8172 ArgLeu Ile Ser Val Ser Ser Glu Gly His Cys Ile Ile Tyr Tyr Glu 2690 26952700 cga ggg cga ttc agt aat ttc agc att aat ggg aaa ctt ttg gct caa8220 Arg Gly Arg Phe Ser Asn Phe Ser Ile Asn Gly Lys Leu Leu Ala Gln2705 2710 2715 2720 atg gag atc aat gat tca aca cgg gcc att ctc ctg agcagt gac ggc 8268 Met Glu Ile Asn Asp Ser Thr Arg Ala Ile Leu Leu Ser SerAsp Gly 2725 2730 2735 cag aac ctg gtc acc gga ggg gac aat ggg gta gtagag gtc tgg cag 8316 Gln Asn Leu Val Thr Gly Gly Asp Asn Gly Val Val GluVal Trp Gln 2740 2745 2750 gcc tgt gac ttc aag caa ctg tac att tac cctgga tgt gat gct ggc 8364 Ala Cys Asp Phe Lys Gln Leu Tyr Ile Tyr Pro GlyCys Asp Ala Gly 2755 2760 2765 att aga gca atg gac ttg tcc cat gac cagagg act ctg atc act ggc 8412 Ile Arg Ala Met Asp Leu Ser His Asp Gln ArgThr Leu Ile Thr Gly 2770 2775 2780 atg gct tct ggt agc att gta gct tttaat ata gat ttt aat cgg tgg 8460 Met Ala Ser Gly Ser Ile Val Ala Phe AsnIle Asp Phe Asn Arg Trp 2785 2790 2795 2800 cat tat gag cat cag aac agatac tgaagataaa ggaagaacca aaagccaagt 8514 His Tyr Glu His Gln Asn ArgTyr 2805 taaagctgag agcacaagtg ctgcatggaa aggcaatatc tctggtggaaaaaactcgtc 8574 tacatcgacc tccgtttgta cattccatca cacccagcaa tagctgtacattgtagtcag 8634 caaccatttt actttgtgtg ttttttcacg actgaacacc agctgctatcaagcaagctt 8694 atatcatgta aattatatga attaggagat gttttggtaa ttatttcatatattgttgtt 8754 tattgagaaa aggttgtagg atgtgtcaca agagactttt gacaattctgaggaaccttg 8814 tgtccagttg ttacaaagtt taagctttga acct 8848 50 2808 PRTHomo sapiens 50 Met Ala Ser Glu Lys Pro Gly Pro Gly Pro Gly Leu Glu ProGln Pro 1 5 10 15 Val Gly Leu Ile Ala Val Gly Ala Ala Gly Gly Gly GlyGly Gly Ser 20 25 30 Gly Gly Gly Gly Thr Gly Gly Ser Gly Met Gly Glu LeuArg Gly Ala 35 40 45 Ser Gly Ser Gly Ser Val Met Leu Pro Ala Gly Met IleAsn Pro Ser 50 55 60 Val Pro Ile Arg Asn Ile Arg Met Lys Phe Ala Val LeuIle Gly Leu 65 70 75 80 Ile Gln Val Gly Glu Val Ser Asn Arg Asp Ile ValGlu Thr Val Leu 85 90 95 Asn Leu Leu Val Gly Gly Glu Phe Asp Leu Glu MetAsn Phe Ile Ile 100 105 110 Gln Asp Ala Glu Ser Ile Thr Cys Met Thr GluLeu Leu Glu His Cys 115 120 125 Asp Val Thr Cys Gln Ala Glu Ile Trp SerMet Phe Thr Ala Ile Leu 130 135 140 Arg Lys Ser Val Arg Asn Leu Gln ThrSer Thr Glu Val Gly Leu Ile 145 150 155 160 Glu Gln Val Leu Leu Lys MetSer Ala Val Asp Asp Met Ile Ala Asp 165 170 175 Leu Leu Val Asp Met LeuGly Val Leu Ala Ser Tyr Ser Ile Thr Val 180 185 190 Lys Glu Leu Lys LeuLeu Phe Ser Met Leu Arg Gly Glu Ser Gly Ile 195 200 205 Trp Pro Arg HisAla Val Lys Leu Leu Ser Val Leu Asn Gln Met Pro 210 215 220 Gln Arg HisGly Pro Asp Thr Phe Phe Asn Phe Pro Gly Cys Ser Ala 225 230 235 240 AlaAla Ile Ala Leu Pro Pro Ile Ala Lys Trp Pro Tyr Gln Asn Gly 245 250 255Phe Thr Leu Asn Thr Trp Phe Arg Met Asp Pro Leu Asn Asn Ile Asn 260 265270 Val Asp Lys Asp Lys Pro Tyr Leu Tyr Cys Phe Arg Thr Ser Lys Gly 275280 285 Val Gly Tyr Ser Ala His Phe Val Gly Asn Cys Leu Ile Val Thr Ser290 295 300 Leu Lys Ser Lys Gly Lys Gly Phe Gln His Cys Val Lys Tyr AspPhe 305 310 315 320 Gln Pro Arg Lys Trp Tyr Met Ile Ser Ile Val His IleTyr Asn Arg 325 330 335 Trp Arg Asn Ser Glu Ile Arg Cys Tyr Val Asn GlyGln Leu Val Ser 340 345 350 Tyr Gly Asp Met Ala Trp His Val Asn Thr AsnAsp Ser Tyr Asp Lys 355 360 365 Cys Phe Leu Gly Ser Ser Glu Thr Ala AspAla Asn Arg Val Phe Cys 370 375 380 Gly Gln Leu Gly Ala Val Tyr Val PheSer Glu Ala Leu Asn Pro Ala 385 390 395 400 Gln Ile Phe Ala Ile His GlnLeu Gly Pro Gly Tyr Lys Ser Thr Phe 405 410 415 Lys Phe Lys Ser Glu SerAsp Ile His Leu Ala Glu His His Lys Gln 420 425 430 Val Leu Tyr Asp GlyLys Leu Ala Ser Ser Ile Ala Phe Thr Tyr Asn 435 440 445 Ala Lys Ala ThrAsp Ala Gln Leu Cys Leu Glu Ser Ser Pro Lys Glu 450 455 460 Asn Ala SerIle Phe Val His Ser Pro His Ala Leu Met Leu Gln Asp 465 470 475 480 ValLys Ala Ile Val Thr His Ser Ile His Ser Ala Ile His Ser Ile 485 490 495Gly Gly Ile Gln Val Leu Phe Pro Leu Phe Ala Gln Leu Asp Asn Arg 500 505510 Gln Leu Asn Asp Ser Gln Val Glu Thr Thr Val Ala Thr Leu Leu Ala 515520 525 Phe Leu Val Glu Leu Leu Lys Ser Ser Val Ala Met Gln Glu Gln Met530 535 540 Leu Gly Gly Lys Gly Phe Leu Val Ile Gly Tyr Leu Leu Glu LysSer 545 550 555 560 Ser Arg Val His Ile Thr Arg Ala Val Leu Glu Gln PheLeu Ser Phe 565 570 575 Ala Lys Tyr Leu Asp Gly Leu Ser His Gly Ala ProLeu Leu Lys Gln 580 585 590 Leu Cys Asp His Ile Leu Phe Asn Pro Ala IleTrp Ile His Thr Pro 595 600 605 Ala Lys Val Gln Leu Ser Leu Tyr Thr TyrLeu Ser Ala Glu Phe Ile 610 615 620 Gly Thr Ala Thr Ile Tyr Thr Thr IleArg Arg Val Gly Thr Val Leu 625 630 635 640 Gln Leu Met His Thr Leu LysTyr Tyr Tyr Trp Val Ile Asn Pro Ala 645 650 655 Asp Ser Ser Gly Ile ThrPro Lys Gly Leu Asp Gly Pro Arg Pro Ser 660 665 670 Gln Lys Glu Ile IleSer Leu Arg Ala Phe Met Leu Leu Phe Leu Lys 675 680 685 Gln Leu Ile LeuLys Asp Arg Gly Val Lys Glu Asp Glu Leu Gln Ser 690 695 700 Ile Leu AsnTyr Leu Leu Thr Met His Glu Asp Glu Asn Ile His Asp 705 710 715 720 ValLeu Gln Leu Leu Val Ala Leu Met Ser Glu His Pro Ala Ser Met 725 730 735Ile Pro Ala Phe Asp Gln Arg Asn Gly Ile Arg Val Ile Tyr Lys Leu 740 745750 Leu Ala Ser Lys Ser Glu Ser Ile Trp Val Gln Ala Leu Lys Val Leu 755760 765 Gly Tyr Phe Leu Lys His Leu Gly His Lys Arg Lys Val Glu Ile Met770 775 780 His Thr His Ser Leu Phe Thr Leu Leu Gly Glu Arg Leu Met LeuHis 785 790 795 800 Thr Asn Thr Val Thr Val Thr Thr Tyr Asn Thr Leu TyrGlu Ile Leu 805 810 815 Thr Glu Gln Val Cys Thr Gln Val Val His Lys ProHis Pro Glu Pro 820 825 830 Asp Ser Thr Val Lys Ile Gln Asn Pro Met IleLeu Lys Val Val Ala 835 840 845 Thr Leu Leu Lys Asn Ser Thr Pro Ser AlaGlu Leu Met Glu Val Arg 850 855 860 Arg Leu Phe Leu Ser Asp Met Ile LysLeu Phe Ser Asn Ser Arg Glu 865 870 875 880 Asn Arg Arg Cys Leu Leu GlnCys Ser Val Trp Gln Asp Trp Met Phe 885 890 895 Ser Leu Gly Tyr Ile AsnPro Lys Asn Ser Glu Glu Gln Lys Ile Thr 900 905 910 Glu Met Val Tyr AsnIle Phe Arg Ile Leu Leu Tyr His Ala Ile Lys 915 920 925 Tyr Glu Trp GlyGly Trp Arg Val Trp Val Asp Thr Leu Ser Ile Ala 930 935 940 His Ser LysVal Thr Tyr Glu Ala His Lys Glu Tyr Leu Ala Lys Met 945 950 955 960 TyrGlu Glu Tyr Gln Arg Gln Glu Glu Glu Asn Ile Lys Lys Gly Lys 965 970 975Lys Gly Asn Val Ser Thr Ile Ser Gly Leu Ser Ser Gln Thr Thr Gly 980 985990 Ala Lys Gly Gly Met Glu Ile Arg Glu Ile Glu Asp Leu Ser Gln Ser 9951000 1005 Gln Ser Pro Glu Ser Glu Thr Asp Tyr Pro Val Ser Thr Asp ThrArg 1010 1015 1020 Asp Leu Leu Met Ser Thr Lys Val Ser Asp Asp Ile LeuGly Asn Ser 1025 1030 1035 1040 Asp Arg Pro Gly Ser Gly Val His Val GluVal His Asp Leu Leu Val 1045 1050 1055 Asp Ile Lys Ala Glu Lys Val GluAla Thr Glu Val Lys Leu Asp Asp 1060 1065 1070 Met Asp Leu Ser Pro GluThr Leu Val Gly Gly Glu Asn Gly Ala Leu 1075 1080 1085 Val Glu Val GluSer Leu Leu Asp Asn Val Tyr Ser Ala Ala Val Glu 1090 1095 1100 Lys LeuGln Asn Asn Val His Gly Ser Val Gly Ile Ile Lys Lys Asn 1105 1110 11151120 Glu Glu Lys Asp Asn Gly Pro Leu Ile Thr Leu Ala Asp Glu Lys Glu1125 1130 1135 Asp Leu Pro Asn Ser Ser Thr Ser Phe Leu Phe Asp Lys IlePro Lys 1140 1145 1150 Gln Glu Glu Lys Leu Leu Pro Glu Leu Ser Ser AsnHis Ile Ile Pro 1155 1160 1165 Asn Ile Gln Asp Thr Gln Val His Leu GlyVal Ser Asp Asp Leu Gly 1170 1175 1180 Leu Leu Ala His Met Thr Gly SerVal Asp Leu Thr Cys Thr Ser Ser 1185 1190 1195 1200 Ile Ile Glu Glu LysGlu Phe Lys Ile His Thr Thr Ser Asp Gly Met 1205 1210 1215 Ser Ser IleSer Glu Arg Asp Leu Ala Ser Ser Thr Lys Gly Leu Glu 1220 1225 1230 TyrAla Glu Met Thr Ala Thr Thr Leu Glu Thr Glu Ser Ser Ser Ser 1235 12401245 Lys Ile Val Pro Asn Ile Asp Ala Gly Ser Ile Ile Ser Asp Thr Glu1250 1255 1260 Arg Ser Asp Asp Gly Lys Glu Ser Gly Lys Glu Ile Arg LysIle Gln 1265 1270 1275 1280 Thr Thr Thr Thr Thr Gln Gly Arg Ser Ile ThrGln Gln Asp Arg Asp 1285 1290 1295 Leu Arg Val Asp Leu Gly Phe Arg GlyMet Pro Met Thr Glu Glu Gln 1300 1305 1310 Arg Arg Gln Phe Ser Pro GlyPro Arg Thr Thr Met Phe Arg Ile Pro 1315 1320 1325 Glu Phe Lys Trp SerPro Met His Gln Arg Leu Leu Thr Asp Leu Leu 1330 1335 1340 Phe Ala LeuGlu Thr Asp Val His Val Trp Arg Ser His Ser Thr Lys 1345 1350 1355 1360Ser Val Met Asp Phe Val Asn Ser Asn Glu Asn Ile Ile Phe Val His 13651370 1375 Asn Thr Ile His Leu Ile Ser Gln Met Val Asp Asn Ile Ile IleAla 1380 1385 1390 Cys Gly Gly Ile Leu Pro Leu Leu Ser Ala Ala Thr SerPro Thr Gly 1395 1400 1405 Ser Lys Thr Glu Leu Glu Asn Ile Glu Val ThrGln Gly Met Ser Ala 1410 1415 1420 Glu Thr Ala Val Thr Phe Leu Ser ArgLeu Met Ala Met Val Asp Val 1425 1430 1435 1440 Leu Val Phe Ala Ser SerLeu Asn Phe Ser Glu Ile Glu Ala Glu Lys 1445 1450 1455 Asn Met Ser SerGly Gly Leu Met Arg Gln Cys Leu Arg Leu Val Cys 1460 1465 1470 Cys ValAla Val Arg Asn Cys Leu Glu Cys Arg Gln Arg Gln Arg Asp 1475 1480 1485Arg Gly Asn Lys Ser Ser His Gly Ser Ser Lys Pro Gln Glu Val Pro 14901495 1500 Gln Ser Thr Pro Leu Glu Asn Val Pro Gly Asn Leu Ser Pro IleLys 1505 1510 1515 1520 Asp Pro Asp Arg Leu Leu Gln Asp Val Asp Ile AsnArg Leu Arg Ala 1525 1530 1535 Val Val Phe Arg Asp Val Asp Asp Ser LysGln Ala Gln Phe Leu Ala 1540 1545 1550 Leu Ala Val Val Tyr Phe Ile SerVal Leu Met Val Ser Lys Tyr Arg 1555 1560 1565 Asp Ile Leu Glu Pro GlnArg Glu Thr Thr Arg Thr Gly Ser Gln Pro 1570 1575 1580 Gly Arg Asn IleArg Gln Glu Ile Asn Ser Pro Thr Ser Thr Glu Thr 1585 1590 1595 1600 ProAla Ala Phe Pro Asp Thr Ile Lys Glu Lys Glu Thr Pro Thr Pro 1605 16101615 Gly Glu Asp Ile Gln Val Glu Ser Ser Ile Pro His Thr Asp Ser Gly1620 1625 1630 Ile Gly Glu Glu Gln Val Ala Ser Ile Leu Asn Gly Ala GluLeu Glu 1635 1640 1645 Thr Ser Thr Gly Pro Asp Ala Met Ser Glu Leu LeuSer Thr Leu Ser 1650 1655 1660 Ser Glu Val Lys Lys Ser Gln Glu Ser LeuThr Glu Asn Pro Ser Glu 1665 1670 1675 1680 Thr Leu Lys Pro Ala Thr SerIle Ser Ser Ile Ser Gln Thr Lys Gly 1685 1690 1695 Ile Asn Val Lys GluIle Leu Lys Ser Leu Val Ala Ala Pro Val Glu 1700 1705 1710 Ile Ala GluCys Gly Pro Glu Pro Ile Pro Tyr Pro Asp Pro Ala Leu 1715 1720 1725 LysArg Glu Thr Gln Ala Ile Leu Pro Met Gln Phe His Ser Phe Asp 1730 17351740 Ser Ile Thr Ala Lys Leu Glu Arg Ala Leu Glu Lys Val Ala Pro Leu1745 1750 1755 1760 Leu Arg Glu Ile Phe Val Asp Phe Ala Pro Phe Leu SerArg Thr Leu 1765 1770 1775 Leu Gly Ser His Gly Gln Glu Leu Leu Ile GluGly Leu Val Cys Met 1780 1785 1790 Lys Ser Ser Thr Ser Val Val Glu LeuVal Met Leu Leu Cys Ser Gln 1795 1800 1805 Glu Trp Gln Asn Ser Ile GlnLys Asn Ala Gly Leu Ala Phe Ile Glu 1810 1815 1820 Leu Ile Asn Glu GlyArg Leu Leu Cys His Ala Met Lys Asp His Ile 1825 1830 1835 1840 Val ArgVal Ala Asn Glu Ala Glu Phe Ile Leu Asn Arg Gln Arg Ala 1845 1850 1855Glu Asp Val His Lys His Ala Glu Phe Glu Ser Gln Cys Ala Gln Tyr 18601865 1870 Ala Ala Asp Arg Arg Glu Glu Glu Lys Met Cys Asp His Leu IleSer 1875 1880 1885 Ala Ala Lys His Arg Asp His Val Thr Ala Asn Gln LeuLys Gln Lys 1890 1895 1900 Ile Leu Asn Ile Leu Thr Asn Lys His Gly AlaTrp Gly Ala Val Ser 1905 1910 1915 1920 His Ser Gln Leu His Asp Phe TrpArg Leu Asp Tyr Trp Glu Asp Asp 1925 1930 1935 Leu Arg Arg Arg Arg ArgPhe Val Arg Asn Ala Phe Gly Ser Thr His 1940 1945 1950 Ala Glu Ala LeuLeu Lys Ala Ala Ile Glu Tyr Gly Thr Glu Glu Asp 1955 1960 1965 Val ValLys Ser Lys Lys Thr Phe Arg Ser Gln Ala Ile Val Asn Gln 1970 1975 1980Asn Ala Glu Thr Glu Leu Met Leu Glu Gly Asp Asp Asp Ala Val Ser 19851990 1995 2000 Leu Leu Gln Glu Lys Glu Ile Asp Asn Leu Ala Gly Pro ValVal Leu 2005 2010 2015 Ser Thr Pro Ala Gln Leu Ile Ala Pro Val Val ValAla Lys Gly Thr 2020 2025 2030 Leu Ser Ile Thr Thr Thr Glu Ile Tyr PheGlu Val Asp Glu Asp Asp 2035 2040 2045 Ser Ala Phe Lys Lys Ile Asp ThrLys Val Leu Ala Tyr Thr Glu Gly 2050 2055 2060 Leu His Gly Lys Trp MetPhe Ser Glu Ile Arg Ala Val Phe Ser Arg 2065 2070 2075 2080 Arg Tyr LeuLeu Gln Asn Thr Ala Leu Glu Val Phe Met Ala Asn Arg 2085 2090 2095 ThrSer Val Met Phe Asn Phe Pro Asp Gln Ala Thr Val Lys Lys Val 2100 21052110 Val Tyr Ser Leu Pro Arg Val Gly Val Gly Thr Ser Tyr Gly Leu Pro2115 2120 2125 Gln Ala Arg Arg Ile Ser Leu Ala Thr Pro Arg Gln Leu TyrLys Ser 2130 2135 2140 Ser Asn Met Thr Gln Arg Trp Gln Arg Arg Glu IleSer Asn Phe Glu 2145 2150 2155 2160 Tyr Leu Met Phe Leu Asn Thr Ile AlaGly Arg Thr Tyr Asn Asp Leu 2165 2170 2175 Asn Gln Tyr Pro Val Phe ProTrp Val Leu Thr Asn Tyr Glu Ser Glu 2180 2185 2190 Glu Leu Asp Leu ThrLeu Pro Gly Asn Phe Arg Asp Leu Ser Lys Pro 2195 2200 2205 Ile Gly AlaLeu Asn Pro Lys Arg Ala Val Phe Tyr Ala Glu Arg Tyr 2210 2215 2220 GluThr Trp Glu Asp Asp Gln Ser Pro Pro Tyr His Tyr Asn Thr His 2225 22302235 2240 Tyr Ser Thr Ala Thr Ser Thr Leu Ser Trp Leu Val Arg Ile GluPro 2245 2250 2255 Phe Thr Thr Phe Phe Leu Asn Ala Asn Asp Gly Lys PheAsp His Pro 2260 2265 2270 Asp Arg Thr Phe Ser Ser Val Ala Arg Ser TrpArg Thr Ser Gln Arg 2275 2280 2285 Asp Thr Ser Asp Val Lys Glu Leu IlePro Glu Phe Tyr Tyr Leu Pro 2290 2295 2300 Glu Met Phe Val Asn Ser AsnGly Tyr Asn Leu Gly Val Arg Glu Asp 2305 2310 2315 2320 Glu Val Val ValAsn Asp Val Asp Leu Pro Pro Trp Ala Lys Lys Pro 2325 2330 2335 Glu AspPhe Val Arg Ile Asn Arg Met Ala Leu Glu Ser Glu Phe Val 2340 2345 2350Ser Cys Gln Leu His Gln Trp Ile Asp Leu Ile Phe Gly Tyr Lys Gln 23552360 2365 Arg Gly Pro Glu Ala Val Arg Ala Leu Asn Val Phe His Tyr LeuThr 2370 2375 2380 Tyr Glu Gly Ser Val Asn Leu Asp Ser Ile Thr Asp ProVal Leu Arg 2385 2390 2395 2400 Glu Ala Met Glu Ala Gln Ile Gln Asn PheGly Gln Thr Pro Ser Gln 2405 2410 2415 Leu Leu Ile Glu Pro His Pro ProArg Ser Ser Ala Met His Leu Cys 2420 2425 2430 Phe Leu Pro Gln Ser ProLeu Met Phe Lys Asp Gln Met Gln Gln Asp 2435 2440 2445 Val Ile Met ValLeu Lys Phe Pro Ser Asn Ser Pro Val Thr His Val 2450 2455 2460 Ala AlaAsn Thr Leu Pro His Leu Thr Ile Pro Ala Val Val Thr Val 2465 2470 24752480 Thr Cys Ser Arg Leu Phe Ala Val Asn Arg Trp His Asn Thr Val Gly2485 2490 2495 Leu Arg Gly Ala Pro Gly Tyr Ser Leu Asp Gln Ala His HisLeu Pro 2500 2505 2510 Ile Glu Met Asp Pro Leu Ile Ala Asn Asn Ser GlyVal Asn Lys Arg 2515 2520 2525 Gln Ile Thr Asp Leu Val Asp Gln Ser IleGln Ile Asn Ala His Cys 2530 2535 2540 Phe Val Val Thr Ala Asp Asn ArgTyr Ile Leu Ile Cys Gly Phe Trp 2545 2550 2555 2560 Asp Lys Ser Phe ArgVal Tyr Ser Thr Glu Thr Gly Lys Leu Thr Gln 2565 2570 2575 Ile Val PheGly His Trp Asp Val Val Thr Cys Leu Ala Arg Ser Glu 2580 2585 2590 SerTyr Ile Gly Gly Asp Cys Tyr Ile Val Ser Gly Ser Arg Asp Ala 2595 26002605 Thr Leu Leu Leu Trp Tyr Trp Ser Gly Arg His His Ile Ile Gly Asp2610 2615 2620 Asn Pro Asn Ser Ser Asp Tyr Pro Ala Pro Arg Ala Val LeuThr Gly 2625 2630 2635 2640 His Asp His Glu Val Val Cys Val Ser Val CysAla Glu Leu Gly Leu 2645 2650 2655 Val Ile Ser Gly Ala Lys Glu Gly ProCys Leu Val His Thr Ile Thr 2660 2665 2670 Gly Asp Leu Leu Arg Ala LeuGlu Gly Pro Glu Asn Cys Leu Phe Pro 2675 2680 2685 Arg Leu Ile Ser ValSer Ser Glu Gly His Cys Ile Ile Tyr Tyr Glu 2690 2695 2700 Arg Gly ArgPhe Ser Asn Phe Ser Ile Asn Gly Lys Leu Leu Ala Gln 2705 2710 2715 2720Met Glu Ile Asn Asp Ser Thr Arg Ala Ile Leu Leu Ser Ser Asp Gly 27252730 2735 Gln Asn Leu Val Thr Gly Gly Asp Asn Gly Val Val Glu Val TrpGln 2740 2745 2750 Ala Cys Asp Phe Lys Gln Leu Tyr Ile Tyr Pro Gly CysAsp Ala Gly 2755 2760 2765 Ile Arg Ala Met Asp Leu Ser His Asp Gln ArgThr Leu Ile Thr Gly 2770 2775 2780 Met Ala Ser Gly Ser Ile Val Ala PheAsn Ile Asp Phe Asn Arg Trp 2785 2790 2795 2800 His Tyr Glu His Gln AsnArg Tyr 2805 51 2687 DNA Homo sapiens CDS (59)..(2650) 51 acaagctccacagagccgcg ggaggacggt tgcctggtat tattagcaag cagcaaat 58 atg gcg gtg gcgcgc gtg gac gcg gct ttg cct ccc gga gaa ggt tca 106 Met Ala Val Ala ArgVal Asp Ala Ala Leu Pro Pro Gly Glu Gly Ser 1 5 10 15 gtg gtc aat tggtca gga cag gga cta cag aaa tta ggt cca aat tta 154 Val Val Asn Trp SerGly Gln Gly Leu Gln Lys Leu Gly Pro Asn Leu 20 25 30 ccc tgt gaa gct gatatt cac act ttg att ctg gat aaa aat cag att 202 Pro Cys Glu Ala Asp IleHis Thr Leu Ile Leu Asp Lys Asn Gln Ile 35 40 45 att aaa ttg gaa aat ctggag aaa tgc aaa cga tta ata cag tta tca 250 Ile Lys Leu Glu Asn Leu GluLys Cys Lys Arg Leu Ile Gln Leu Ser 50 55 60 gta gct aat aat cgg ctg gttcgg atg atg ggt gtg gcc aag ctg acg 298 Val Ala Asn Asn Arg Leu Val ArgMet Met Gly Val Ala Lys Leu Thr 65 70 75 80 ttg ctt cgt gta tta aat ttgcct cat aat agc att ggc tgt gtg gaa 346 Leu Leu Arg Val Leu Asn Leu ProHis Asn Ser Ile Gly Cys Val Glu 85 90 95 ggg cta aag gaa cta gta cat ctggaa tgg ctg aat ttg gca gga aat 394 Gly Leu Lys Glu Leu Val His Leu GluTrp Leu Asn Leu Ala Gly Asn 100 105 110 aat ctt aag gcc atg gaa cag atcaat agc tgc aca gct cta cag cat 442 Asn Leu Lys Ala Met Glu Gln Ile AsnSer Cys Thr Ala Leu Gln His 115 120 125 ctc gat tta tca gac aat aat atatcc cag ata ggt gat cta tct aaa 490 Leu Asp Leu Ser Asp Asn Asn Ile SerGln Ile Gly Asp Leu Ser Lys 130 135 140 ttg gta tcc ctg aaa gta aag accctg ctt tta cat gga aac atc atc 538 Leu Val Ser Leu Lys Val Lys Thr LeuLeu Leu His Gly Asn Ile Ile 145 150 155 160 acc tct ctt aga atg gca cctgct tac cta ccc aga agt ctt gct ata 586 Thr Ser Leu Arg Met Ala Pro AlaTyr Leu Pro Arg Ser Leu Ala Ile 165 170 175 ctt tct ttg gca gaa aat gaaatc cga gac tta aat gag atc tct ttt 634 Leu Ser Leu Ala Glu Asn Glu IleArg Asp Leu Asn Glu Ile Ser Phe 180 185 190 ttg gca tcc tta act gaa ttggaa cag ttg tcg att atg aac aat cct 682 Leu Ala Ser Leu Thr Glu Leu GluGln Leu Ser Ile Met Asn Asn Pro 195 200 205 tgt gtg atg gca aca cca tccatc cca gga ttt gac tat cgg ccg tac 730 Cys Val Met Ala Thr Pro Ser IlePro Gly Phe Asp Tyr Arg Pro Tyr 210 215 220 atc gtc agc tgg tgc cta aacctc aga gtc cta gat gga tat gtg att 778 Ile Val Ser Trp Cys Leu Asn LeuArg Val Leu Asp Gly Tyr Val Ile 225 230 235 240 tct cag aag gaa agt ttgaaa gct gaa tgg ctc tat agt caa ggc aag 826 Ser Gln Lys Glu Ser Leu LysAla Glu Trp Leu Tyr Ser Gln Gly Lys 245 250 255 ggg aga gca tat cgg cctggc cag cac atc cag ctt gtc caa tat ctg 874 Gly Arg Ala Tyr Arg Pro GlyGln His Ile Gln Leu Val Gln Tyr Leu 260 265 270 gct aca gtc tgc ccc ctcact tct aca cta ggt ctt caa act gca gag 922 Ala Thr Val Cys Pro Leu ThrSer Thr Leu Gly Leu Gln Thr Ala Glu 275 280 285 gat gcc aaa cta gac aagatt ttg agc aaa cag agg ttt cac cag agg 970 Asp Ala Lys Leu Asp Lys IleLeu Ser Lys Gln Arg Phe His Gln Arg 290 295 300 cag ttg atg aac caa agccaa aat gaa gag ttg tct cct ctt gtt cct 1018 Gln Leu Met Asn Gln Ser GlnAsn Glu Glu Leu Ser Pro Leu Val Pro 305 310 315 320 gtt gaa aca agg gcatcc ctt att cct gag cat tca agc cct gtt caa 1066 Val Glu Thr Arg Ala SerLeu Ile Pro Glu His Ser Ser Pro Val Gln 325 330 335 gat tgc cag ata tccgaa ccc gtc att caa gtg aat tct tgg gtt ggg 1114 Asp Cys Gln Ile Ser GluPro Val Ile Gln Val Asn Ser Trp Val Gly 340 345 350 ata aac agt aat gatgat cag tta ttt gcg gtt aag aat aat ttt cca 1162 Ile Asn Ser Asn Asp AspGln Leu Phe Ala Val Lys Asn Asn Phe Pro 355 360 365 gcc tct agt cac actacg aga tat tct cga aat gat ctg cac ctg gaa 1210 Ala Ser Ser His Thr ThrArg Tyr Ser Arg Asn Asp Leu His Leu Glu 370 375 380 gac ata cag acg gatgag gac aag tta aac tgt agt ctt ctc tct tca 1258 Asp Ile Gln Thr Asp GluAsp Lys Leu Asn Cys Ser Leu Leu Ser Ser 385 390 395 400 gag tct act tttatg cca gtt gca tca gga ctg tct cca cta tca cct 1306 Glu Ser Thr Phe MetPro Val Ala Ser Gly Leu Ser Pro Leu Ser Pro 405 410 415 aca gtt gag ctgagg ctg cag ggc att aac ttg ggc cta gaa gat gat 1354 Thr Val Glu Leu ArgLeu Gln Gly Ile Asn Leu Gly Leu Glu Asp Asp 420 425 430 ggt gtt gca gatgaa tct gtg aaa ggg ctg gaa agc cag gtg ttg gat 1402 Gly Val Ala Asp GluSer Val Lys Gly Leu Glu Ser Gln Val Leu Asp 435 440 445 aag gaa gag gaacag cct tta tgg gct gca aat gag aat tct gtt caa 1450 Lys Glu Glu Glu GlnPro Leu Trp Ala Ala Asn Glu Asn Ser Val Gln 450 455 460 atg atg aga agtgaa atc aat aca gag gta aat gag aaa gct gga cta 1498 Met Met Arg Ser GluIle Asn Thr Glu Val Asn Glu Lys Ala Gly Leu 465 470 475 480 tta cct tgtcct gag cca aca ata atc agt gct atc ttg aag gat gat 1546 Leu Pro Cys ProGlu Pro Thr Ile Ile Ser Ala Ile Leu Lys Asp Asp 485 490 495 aac cac agtctt aca ttt ttt cct gag tca act gag cag aaa caa tca 1594 Asn His Ser LeuThr Phe Phe Pro Glu Ser Thr Glu Gln Lys Gln Ser 500 505 510 gac ata aagaaa cca gaa aat aca caa cca gaa aat aaa gaa acc ata 1642 Asp Ile Lys LysPro Glu Asn Thr Gln Pro Glu Asn Lys Glu Thr Ile 515 520 525 tct caa gcaact tca gag aaa ctt ccc atg att tta acc cag aga tct 1690 Ser Gln Ala ThrSer Glu Lys Leu Pro Met Ile Leu Thr Gln Arg Ser 530 535 540 gtt gct ttggga caa gac aaa gtt gcc ctt cag aaa tta aat gat gca 1738 Val Ala Leu GlyGln Asp Lys Val Ala Leu Gln Lys Leu Asn Asp Ala 545 550 555 560 gcc accaag ctt cag gcc tgt tgg cgg gga ttt tat gcc agg aac tac 1786 Ala Thr LysLeu Gln Ala Cys Trp Arg Gly Phe Tyr Ala Arg Asn Tyr 565 570 575 aac cctcaa gcc aaa gat gtg cgt tac gaa atc cgg cta cgc aga atg 1834 Asn Pro GlnAla Lys Asp Val Arg Tyr Glu Ile Arg Leu Arg Arg Met 580 585 590 caa gagcac att gtc tgc tta act gat gaa ata agg aga tta cga aaa 1882 Gln Glu HisIle Val Cys Leu Thr Asp Glu Ile Arg Arg Leu Arg Lys 595 600 605 gaa agagat gaa gaa cgt att aaa aaa ttt gta caa gaa gaa gct ttc 1930 Glu Arg AspGlu Glu Arg Ile Lys Lys Phe Val Gln Glu Glu Ala Phe 610 615 620 aga ttcctt tgg aac cag gta agg tct cta cag gtt tgg caa cag aca 1978 Arg Phe LeuTrp Asn Gln Val Arg Ser Leu Gln Val Trp Gln Gln Thr 625 630 635 640 gtggac cag cgt cta agt tcc tgg cat act gat gtt caa caa ata tca 2026 Val AspGln Arg Leu Ser Ser Trp His Thr Asp Val Gln Gln Ile Ser 645 650 655 agtact ctt gtg cca tcg aaa cat cca tta ttt acc caa agc cag gag 2074 Ser ThrLeu Val Pro Ser Lys His Pro Leu Phe Thr Gln Ser Gln Glu 660 665 670 tcctct tgt gat caa aat gct gat tgg ttt att gct tct gat gta gct 2122 Ser SerCys Asp Gln Asn Ala Asp Trp Phe Ile Ala Ser Asp Val Ala 675 680 685 cctcaa gag aaa tca tta cca gaa ttt cca gac tct ggt ttt cat tcc 2170 Pro GlnGlu Lys Ser Leu Pro Glu Phe Pro Asp Ser Gly Phe His Ser 690 695 700 tctcta aca gaa caa gtt cat tca ttg cag cat tct ttg gat ttt gag 2218 Ser LeuThr Glu Gln Val His Ser Leu Gln His Ser Leu Asp Phe Glu 705 710 715 720aaa agt tcc aca gaa ggc agt gaa agc tcc ata atg ggg aat tcc att 2266 LysSer Ser Thr Glu Gly Ser Glu Ser Ser Ile Met Gly Asn Ser Ile 725 730 735gac aca gtc aga tat ggc aaa gaa tca gat tta ggg gat gtt agt gaa 2314 AspThr Val Arg Tyr Gly Lys Glu Ser Asp Leu Gly Asp Val Ser Glu 740 745 750gaa cat ggt gaa tgg aat aag gaa agc tca aat aac gag cag gac aat 2362 GluHis Gly Glu Trp Asn Lys Glu Ser Ser Asn Asn Glu Gln Asp Asn 755 760 765agt ctg ctt gaa cag tat tta act tca gtt caa cag ctg gaa gat gct 2410 SerLeu Leu Glu Gln Tyr Leu Thr Ser Val Gln Gln Leu Glu Asp Ala 770 775 780gat gag agg acc aat ttt gat aca gag aca aga gat agc aaa ctt cac 2458 AspGlu Arg Thr Asn Phe Asp Thr Glu Thr Arg Asp Ser Lys Leu His 785 790 795800 att gct tgt ttc cca gta cag tta gat aca ttg tct gac ggt gct tct 2506Ile Ala Cys Phe Pro Val Gln Leu Asp Thr Leu Ser Asp Gly Ala Ser 805 810815 gta gat gag agt cat ggc ata tct cct cct ttg caa ggt gaa att agc 2554Val Asp Glu Ser His Gly Ile Ser Pro Pro Leu Gln Gly Glu Ile Ser 820 825830 cag aca caa gag aat tct aaa tta aat gca gaa gtt cag ggg cag cag 2602Gln Thr Gln Glu Asn Ser Lys Leu Asn Ala Glu Val Gln Gly Gln Gln 835 840845 cca gaa tgt gat tct aca ttt cag cta ttg cat gtt ggt gtt act gtg 2650Pro Glu Cys Asp Ser Thr Phe Gln Leu Leu His Val Gly Val Thr Val 850 855860 tagcatgtct tttgggaggc agatatccac ttaactt 2687 52 864 PRT Homosapiens 52 Met Ala Val Ala Arg Val Asp Ala Ala Leu Pro Pro Gly Glu GlySer 1 5 10 15 Val Val Asn Trp Ser Gly Gln Gly Leu Gln Lys Leu Gly ProAsn Leu 20 25 30 Pro Cys Glu Ala Asp Ile His Thr Leu Ile Leu Asp Lys AsnGln Ile 35 40 45 Ile Lys Leu Glu Asn Leu Glu Lys Cys Lys Arg Leu Ile GlnLeu Ser 50 55 60 Val Ala Asn Asn Arg Leu Val Arg Met Met Gly Val Ala LysLeu Thr 65 70 75 80 Leu Leu Arg Val Leu Asn Leu Pro His Asn Ser Ile GlyCys Val Glu 85 90 95 Gly Leu Lys Glu Leu Val His Leu Glu Trp Leu Asn LeuAla Gly Asn 100 105 110 Asn Leu Lys Ala Met Glu Gln Ile Asn Ser Cys ThrAla Leu Gln His 115 120 125 Leu Asp Leu Ser Asp Asn Asn Ile Ser Gln IleGly Asp Leu Ser Lys 130 135 140 Leu Val Ser Leu Lys Val Lys Thr Leu LeuLeu His Gly Asn Ile Ile 145 150 155 160 Thr Ser Leu Arg Met Ala Pro AlaTyr Leu Pro Arg Ser Leu Ala Ile 165 170 175 Leu Ser Leu Ala Glu Asn GluIle Arg Asp Leu Asn Glu Ile Ser Phe 180 185 190 Leu Ala Ser Leu Thr GluLeu Glu Gln Leu Ser Ile Met Asn Asn Pro 195 200 205 Cys Val Met Ala ThrPro Ser Ile Pro Gly Phe Asp Tyr Arg Pro Tyr 210 215 220 Ile Val Ser TrpCys Leu Asn Leu Arg Val Leu Asp Gly Tyr Val Ile 225 230 235 240 Ser GlnLys Glu Ser Leu Lys Ala Glu Trp Leu Tyr Ser Gln Gly Lys 245 250 255 GlyArg Ala Tyr Arg Pro Gly Gln His Ile Gln Leu Val Gln Tyr Leu 260 265 270Ala Thr Val Cys Pro Leu Thr Ser Thr Leu Gly Leu Gln Thr Ala Glu 275 280285 Asp Ala Lys Leu Asp Lys Ile Leu Ser Lys Gln Arg Phe His Gln Arg 290295 300 Gln Leu Met Asn Gln Ser Gln Asn Glu Glu Leu Ser Pro Leu Val Pro305 310 315 320 Val Glu Thr Arg Ala Ser Leu Ile Pro Glu His Ser Ser ProVal Gln 325 330 335 Asp Cys Gln Ile Ser Glu Pro Val Ile Gln Val Asn SerTrp Val Gly 340 345 350 Ile Asn Ser Asn Asp Asp Gln Leu Phe Ala Val LysAsn Asn Phe Pro 355 360 365 Ala Ser Ser His Thr Thr Arg Tyr Ser Arg AsnAsp Leu His Leu Glu 370 375 380 Asp Ile Gln Thr Asp Glu Asp Lys Leu AsnCys Ser Leu Leu Ser Ser 385 390 395 400 Glu Ser Thr Phe Met Pro Val AlaSer Gly Leu Ser Pro Leu Ser Pro 405 410 415 Thr Val Glu Leu Arg Leu GlnGly Ile Asn Leu Gly Leu Glu Asp Asp 420 425 430 Gly Val Ala Asp Glu SerVal Lys Gly Leu Glu Ser Gln Val Leu Asp 435 440 445 Lys Glu Glu Glu GlnPro Leu Trp Ala Ala Asn Glu Asn Ser Val Gln 450 455 460 Met Met Arg SerGlu Ile Asn Thr Glu Val Asn Glu Lys Ala Gly Leu 465 470 475 480 Leu ProCys Pro Glu Pro Thr Ile Ile Ser Ala Ile Leu Lys Asp Asp 485 490 495 AsnHis Ser Leu Thr Phe Phe Pro Glu Ser Thr Glu Gln Lys Gln Ser 500 505 510Asp Ile Lys Lys Pro Glu Asn Thr Gln Pro Glu Asn Lys Glu Thr Ile 515 520525 Ser Gln Ala Thr Ser Glu Lys Leu Pro Met Ile Leu Thr Gln Arg Ser 530535 540 Val Ala Leu Gly Gln Asp Lys Val Ala Leu Gln Lys Leu Asn Asp Ala545 550 555 560 Ala Thr Lys Leu Gln Ala Cys Trp Arg Gly Phe Tyr Ala ArgAsn Tyr 565 570 575 Asn Pro Gln Ala Lys Asp Val Arg Tyr Glu Ile Arg LeuArg Arg Met 580 585 590 Gln Glu His Ile Val Cys Leu Thr Asp Glu Ile ArgArg Leu Arg Lys 595 600 605 Glu Arg Asp Glu Glu Arg Ile Lys Lys Phe ValGln Glu Glu Ala Phe 610 615 620 Arg Phe Leu Trp Asn Gln Val Arg Ser LeuGln Val Trp Gln Gln Thr 625 630 635 640 Val Asp Gln Arg Leu Ser Ser TrpHis Thr Asp Val Gln Gln Ile Ser 645 650 655 Ser Thr Leu Val Pro Ser LysHis Pro Leu Phe Thr Gln Ser Gln Glu 660 665 670 Ser Ser Cys Asp Gln AsnAla Asp Trp Phe Ile Ala Ser Asp Val Ala 675 680 685 Pro Gln Glu Lys SerLeu Pro Glu Phe Pro Asp Ser Gly Phe His Ser 690 695 700 Ser Leu Thr GluGln Val His Ser Leu Gln His Ser Leu Asp Phe Glu 705 710 715 720 Lys SerSer Thr Glu Gly Ser Glu Ser Ser Ile Met Gly Asn Ser Ile 725 730 735 AspThr Val Arg Tyr Gly Lys Glu Ser Asp Leu Gly Asp Val Ser Glu 740 745 750Glu His Gly Glu Trp Asn Lys Glu Ser Ser Asn Asn Glu Gln Asp Asn 755 760765 Ser Leu Leu Glu Gln Tyr Leu Thr Ser Val Gln Gln Leu Glu Asp Ala 770775 780 Asp Glu Arg Thr Asn Phe Asp Thr Glu Thr Arg Asp Ser Lys Leu His785 790 795 800 Ile Ala Cys Phe Pro Val Gln Leu Asp Thr Leu Ser Asp GlyAla Ser 805 810 815 Val Asp Glu Ser His Gly Ile Ser Pro Pro Leu Gln GlyGlu Ile Ser 820 825 830 Gln Thr Gln Glu Asn Ser Lys Leu Asn Ala Glu ValGln Gly Gln Gln 835 840 845 Pro Glu Cys Asp Ser Thr Phe Gln Leu Leu HisVal Gly Val Thr Val 850 855 860 53 3222 DNA Homo sapiens CDS(61)..(2913) 53 ttcagccctg agaattttga gccacatttg ttgctattat ttttgcatgcacttttcaaa 60 atg att gac tta agc ttc ctg act gaa gag gaa caa gag gccatc atg 108 Met Ile Asp Leu Ser Phe Leu Thr Glu Glu Glu Gln Glu Ala IleMet 1 5 10 15 aag gtt ttg cag cgg gat gct gct ctg aag agg gcc gaa gaagag aga 156 Lys Val Leu Gln Arg Asp Ala Ala Leu Lys Arg Ala Glu Glu GluArg 20 25 30 gtc aga cat ttg cct gaa aaa att aag gat gac cag cag ctg aagaat 204 Val Arg His Leu Pro Glu Lys Ile Lys Asp Asp Gln Gln Leu Lys Asn35 40 45 atg agt ggc caa tgg ttt tat gaa gcc aag gca aaa agg cac agg gac252 Met Ser Gly Gln Trp Phe Tyr Glu Ala Lys Ala Lys Arg His Arg Asp 5055 60 aaa atc cat ggc gca gat atc atc aga gca tct atg aga aag aag agg300 Lys Ile His Gly Ala Asp Ile Ile Arg Ala Ser Met Arg Lys Lys Arg 6570 75 80 ccc cag ata gca gct gag cag agt aaa gac aga gaa aat ggg gca aag348 Pro Gln Ile Ala Ala Glu Gln Ser Lys Asp Arg Glu Asn Gly Ala Lys 8590 95 gaa agc tgg gtg aat aat gtc aac aaa gat gct ttc ctt cct cca gag396 Glu Ser Trp Val Asn Asn Val Asn Lys Asp Ala Phe Leu Pro Pro Glu 100105 110 ctg gct ggc gtt gta gaa gag cca gaa gaa gat gca gca cca gca agc444 Leu Ala Gly Val Val Glu Glu Pro Glu Glu Asp Ala Ala Pro Ala Ser 115120 125 ccg agt tcc agt gtg gta aat cca gct tcc agt gtg att gat atg tcc492 Pro Ser Ser Ser Val Val Asn Pro Ala Ser Ser Val Ile Asp Met Ser 130135 140 cag gaa aac aca agg aaa cca aat gtg tct cca gag aag cag agg aag540 Gln Glu Asn Thr Arg Lys Pro Asn Val Ser Pro Glu Lys Gln Arg Lys 145150 155 160 aat ccg ttt aat agc tcc aag ttg cca gaa ggt cac tca tca caacaa 588 Asn Pro Phe Asn Ser Ser Lys Leu Pro Glu Gly His Ser Ser Gln Gln165 170 175 act aaa aat gaa cag tca aaa aat gga aga act ggt tta ttt cagact 636 Thr Lys Asn Glu Gln Ser Lys Asn Gly Arg Thr Gly Leu Phe Gln Thr180 185 190 tca aaa gag gat gaa ttg tca gag tca aaa gaa aag tca act gtcgca 684 Ser Lys Glu Asp Glu Leu Ser Glu Ser Lys Glu Lys Ser Thr Val Ala195 200 205 gat act tca atc caa aag tta gag aaa tca aag cag act ttg ccaggc 732 Asp Thr Ser Ile Gln Lys Leu Glu Lys Ser Lys Gln Thr Leu Pro Gly210 215 220 ctt tca aat ggg tcc caa atc aag gct cca atc ccc aaa gcc aggaag 780 Leu Ser Asn Gly Ser Gln Ile Lys Ala Pro Ile Pro Lys Ala Arg Lys225 230 235 240 atg atc tac aaa tca act gat tta aac aaa gat gat aac cagtct ttt 828 Met Ile Tyr Lys Ser Thr Asp Leu Asn Lys Asp Asp Asn Gln SerPhe 245 250 255 cct aga caa agg aca gac tcc ctg aaa gcg aga ggg gct ccgaga ggg 876 Pro Arg Gln Arg Thr Asp Ser Leu Lys Ala Arg Gly Ala Pro ArgGly 260 265 270 atc ctc aag cgc aac tcc agt tcc agt agc aca gac tca gaaacc ctt 924 Ile Leu Lys Arg Asn Ser Ser Ser Ser Ser Thr Asp Ser Glu ThrLeu 275 280 285 cgt tat aat cac aac ttt gaa ccc aaa agc aaa att gtg tcacct ggc 972 Arg Tyr Asn His Asn Phe Glu Pro Lys Ser Lys Ile Val Ser ProGly 290 295 300 cta acc atc cat gag aga att tct gag aag gag cat tct ttagaa gac 1020 Leu Thr Ile His Glu Arg Ile Ser Glu Lys Glu His Ser Leu GluAsp 305 310 315 320 aac tct tcc cca aac tcc ctg gag cca tta aag cat gtgaga ttc tct 1068 Asn Ser Ser Pro Asn Ser Leu Glu Pro Leu Lys His Val ArgPhe Ser 325 330 335 gca gtg aag gat gag ctt cca cag agt cct ggg cta atccat ggt cgg 1116 Ala Val Lys Asp Glu Leu Pro Gln Ser Pro Gly Leu Ile HisGly Arg 340 345 350 gaa gta gga gaa ttt agt gtt tta gaa tct gac aga ttgaaa aat gga 1164 Glu Val Gly Glu Phe Ser Val Leu Glu Ser Asp Arg Leu LysAsn Gly 355 360 365 atg gaa gat gca ggg gac aca gaa gag ttt cag agt gaccct aag cct 1212 Met Glu Asp Ala Gly Asp Thr Glu Glu Phe Gln Ser Asp ProLys Pro 370 375 380 tct caa tac aga aag cct tcg ctt ttt cat caa tca acctca agc cca 1260 Ser Gln Tyr Arg Lys Pro Ser Leu Phe His Gln Ser Thr SerSer Pro 385 390 395 400 tat gta tca aaa agt gaa aca cat cag cca atg acttct ggt tct ttt 1308 Tyr Val Ser Lys Ser Glu Thr His Gln Pro Met Thr SerGly Ser Phe 405 410 415 cca att aat ggg ctg cat tct cat tca gaa gtt ttaact gca aga cca 1356 Pro Ile Asn Gly Leu His Ser His Ser Glu Val Leu ThrAla Arg Pro 420 425 430 cag tct atg gag aat tca cca acc atc aat gaa cccaaa gat aaa tca 1404 Gln Ser Met Glu Asn Ser Pro Thr Ile Asn Glu Pro LysAsp Lys Ser 435 440 445 tca gaa tta aca agg ctt gaa tct gta tta ccc agaagc cct gct gat 1452 Ser Glu Leu Thr Arg Leu Glu Ser Val Leu Pro Arg SerPro Ala Asp 450 455 460 gaa ctg tct cat tgt gtt gag cct gag cca tct caggtg cca ggt ggc 1500 Glu Leu Ser His Cys Val Glu Pro Glu Pro Ser Gln ValPro Gly Gly 465 470 475 480 agt tct aga gac cgt cag caa ggt tca gaa gaagaa ccc agt cct gtt 1548 Ser Ser Arg Asp Arg Gln Gln Gly Ser Glu Glu GluPro Ser Pro Val 485 490 495 ttg aaa act ttg gaa agg agt gcc gct agg aaaatg cct tcc aaa agt 1596 Leu Lys Thr Leu Glu Arg Ser Ala Ala Arg Lys MetPro Ser Lys Ser 500 505 510 cta gaa gac att tca tca gat tca tca aat caagca aaa gta gat aat 1644 Leu Glu Asp Ile Ser Ser Asp Ser Ser Asn Gln AlaLys Val Asp Asn 515 520 525 cag cca gaa gaa tta gtg cgt agt gct gaa gatgat gag aaa cca gat 1692 Gln Pro Glu Glu Leu Val Arg Ser Ala Glu Asp AspGlu Lys Pro Asp 530 535 540 cag aag cca gtt aca aat gaa tgc gta cca agaatt tcc aca gtg cct 1740 Gln Lys Pro Val Thr Asn Glu Cys Val Pro Arg IleSer Thr Val Pro 545 550 555 560 aca caa cct gat aat cca ttt tct cac cctgac aaa ctc aaa agg atg 1788 Thr Gln Pro Asp Asn Pro Phe Ser His Pro AspLys Leu Lys Arg Met 565 570 575 agc aag tct gtt cca gca ttt ctc caa gatgag gca gat gac aga gaa 1836 Ser Lys Ser Val Pro Ala Phe Leu Gln Asp GluAla Asp Asp Arg Glu 580 585 590 aca gat aca gca tca gaa agc agt tac cagctc agc aga cac aag aag 1884 Thr Asp Thr Ala Ser Glu Ser Ser Tyr Gln LeuSer Arg His Lys Lys 595 600 605 agc ccg agc tct tta acc aat ctt agc agctcc tct ggc atg acg tcc 1932 Ser Pro Ser Ser Leu Thr Asn Leu Ser Ser SerSer Gly Met Thr Ser 610 615 620 ttg tct tct gtg agt ggc agt gtg atg agtgtt tat agt gga gac ttt 1980 Leu Ser Ser Val Ser Gly Ser Val Met Ser ValTyr Ser Gly Asp Phe 625 630 635 640 ggc aat ctg gaa gtt aaa gga aat attcag ttt gca att gaa tat gtg 2028 Gly Asn Leu Glu Val Lys Gly Asn Ile GlnPhe Ala Ile Glu Tyr Val 645 650 655 gag tca ctg aag gag ttg cat gtt tttgtg gcc cag tgt aag gac tta 2076 Glu Ser Leu Lys Glu Leu His Val Phe ValAla Gln Cys Lys Asp Leu 660 665 670 gca gca gcg gat gta aaa aaa cag cgttca gac cca tat gta aag gcc 2124 Ala Ala Ala Asp Val Lys Lys Gln Arg SerAsp Pro Tyr Val Lys Ala 675 680 685 tat ttg cta cca gac aaa ggc aaa atgggc aag aag aaa aca ctc gta 2172 Tyr Leu Leu Pro Asp Lys Gly Lys Met GlyLys Lys Lys Thr Leu Val 690 695 700 gtg aag aaa acc ttg aat cct gtg tataac gaa ata ctg cgg tat aaa 2220 Val Lys Lys Thr Leu Asn Pro Val Tyr AsnGlu Ile Leu Arg Tyr Lys 705 710 715 720 att gaa aaa caa atc tta aag acacag aaa ttg aac ctg tcc att tgg 2268 Ile Glu Lys Gln Ile Leu Lys Thr GlnLys Leu Asn Leu Ser Ile Trp 725 730 735 cat cgg gat aca ttt aag cgc aatagt ttc cta ggg gag gtg gaa ctt 2316 His Arg Asp Thr Phe Lys Arg Asn SerPhe Leu Gly Glu Val Glu Leu 740 745 750 gat ttg gaa aca tgg gac tgg gataac aaa cag aat aaa caa ttg aga 2364 Asp Leu Glu Thr Trp Asp Trp Asp AsnLys Gln Asn Lys Gln Leu Arg 755 760 765 tgg tac cct ctg aag cgg aag acagca cca gtt gcc ctt gaa gca gaa 2412 Trp Tyr Pro Leu Lys Arg Lys Thr AlaPro Val Ala Leu Glu Ala Glu 770 775 780 aac aga ggt gaa atg aaa cta gctctc cag tat gtc cca gag cca gtc 2460 Asn Arg Gly Glu Met Lys Leu Ala LeuGln Tyr Val Pro Glu Pro Val 785 790 795 800 cct ggt aaa aag ctt cct acaact gga gaa gtg cac atc tgg gtg aag 2508 Pro Gly Lys Lys Leu Pro Thr ThrGly Glu Val His Ile Trp Val Lys 805 810 815 gaa tgc ctt gat cta cca ctgcta agg gga agt cat cta aat tct ttt 2556 Glu Cys Leu Asp Leu Pro Leu LeuArg Gly Ser His Leu Asn Ser Phe 820 825 830 gtt aaa tgt acc atc ctt ccagat aca agt agg aaa agt cgc cag aag 2604 Val Lys Cys Thr Ile Leu Pro AspThr Ser Arg Lys Ser Arg Gln Lys 835 840 845 aca aga gct gta ggg aaa accacc aac cct atc ttc aac cac act atg 2652 Thr Arg Ala Val Gly Lys Thr ThrAsn Pro Ile Phe Asn His Thr Met 850 855 860 gtg tat gat ggg ttc agg cctgaa gat ctg atg gaa gcc tgt gta gag 2700 Val Tyr Asp Gly Phe Arg Pro GluAsp Leu Met Glu Ala Cys Val Glu 865 870 875 880 ctt act gtc tgg gac cattac aaa tta acc aac caa ttt ttg gga ggt 2748 Leu Thr Val Trp Asp His TyrLys Leu Thr Asn Gln Phe Leu Gly Gly 885 890 895 ctt cgt att ggc ttt ggaaca ggt aaa agt tat ggg act gaa gtg gac 2796 Leu Arg Ile Gly Phe Gly ThrGly Lys Ser Tyr Gly Thr Glu Val Asp 900 905 910 tgg atg gac tct act tcagag gaa gtt gct ctc tgg gag aag atg gta 2844 Trp Met Asp Ser Thr Ser GluGlu Val Ala Leu Trp Glu Lys Met Val 915 920 925 aac tcc ccc aat act tggatt gaa gca aca ctg cct ctc aga atg ctt 2892 Asn Ser Pro Asn Thr Trp IleGlu Ala Thr Leu Pro Leu Arg Met Leu 930 935 940 ttg att gcc aag att tccaaa tgagcccaaa ttccactggc tcctccactg 2943 Leu Ile Ala Lys Ile Ser Lys945 950 aaaactacta aaccggtgga atctgatctt gaaaatctga gtaggtggacaaatatcctc 3003 actttctatc tattgcacct aaggaatact acacagcatg taaaagtcaatctgcatgtg 3063 cttctttgat tacaaggccc aagggattta aatataacaa aatgtgtaatttgtgactct 3123 aatattaaat aagatatttg aacaagctag gaaaattgaa tttctgctgctgcttcaaag 3183 aaaaagctgc cccagagcat taaacatggg gtattgtta 3222 54 951PRT Homo sapiens 54 Met Ile Asp Leu Ser Phe Leu Thr Glu Glu Glu Gln GluAla Ile Met 1 5 10 15 Lys Val Leu Gln Arg Asp Ala Ala Leu Lys Arg AlaGlu Glu Glu Arg 20 25 30 Val Arg His Leu Pro Glu Lys Ile Lys Asp Asp GlnGln Leu Lys Asn 35 40 45 Met Ser Gly Gln Trp Phe Tyr Glu Ala Lys Ala LysArg His Arg Asp 50 55 60 Lys Ile His Gly Ala Asp Ile Ile Arg Ala Ser MetArg Lys Lys Arg 65 70 75 80 Pro Gln Ile Ala Ala Glu Gln Ser Lys Asp ArgGlu Asn Gly Ala Lys 85 90 95 Glu Ser Trp Val Asn Asn Val Asn Lys Asp AlaPhe Leu Pro Pro Glu 100 105 110 Leu Ala Gly Val Val Glu Glu Pro Glu GluAsp Ala Ala Pro Ala Ser 115 120 125 Pro Ser Ser Ser Val Val Asn Pro AlaSer Ser Val Ile Asp Met Ser 130 135 140 Gln Glu Asn Thr Arg Lys Pro AsnVal Ser Pro Glu Lys Gln Arg Lys 145 150 155 160 Asn Pro Phe Asn Ser SerLys Leu Pro Glu Gly His Ser Ser Gln Gln 165 170 175 Thr Lys Asn Glu GlnSer Lys Asn Gly Arg Thr Gly Leu Phe Gln Thr 180 185 190 Ser Lys Glu AspGlu Leu Ser Glu Ser Lys Glu Lys Ser Thr Val Ala 195 200 205 Asp Thr SerIle Gln Lys Leu Glu Lys Ser Lys Gln Thr Leu Pro Gly 210 215 220 Leu SerAsn Gly Ser Gln Ile Lys Ala Pro Ile Pro Lys Ala Arg Lys 225 230 235 240Met Ile Tyr Lys Ser Thr Asp Leu Asn Lys Asp Asp Asn Gln Ser Phe 245 250255 Pro Arg Gln Arg Thr Asp Ser Leu Lys Ala Arg Gly Ala Pro Arg Gly 260265 270 Ile Leu Lys Arg Asn Ser Ser Ser Ser Ser Thr Asp Ser Glu Thr Leu275 280 285 Arg Tyr Asn His Asn Phe Glu Pro Lys Ser Lys Ile Val Ser ProGly 290 295 300 Leu Thr Ile His Glu Arg Ile Ser Glu Lys Glu His Ser LeuGlu Asp 305 310 315 320 Asn Ser Ser Pro Asn Ser Leu Glu Pro Leu Lys HisVal Arg Phe Ser 325 330 335 Ala Val Lys Asp Glu Leu Pro Gln Ser Pro GlyLeu Ile His Gly Arg 340 345 350 Glu Val Gly Glu Phe Ser Val Leu Glu SerAsp Arg Leu Lys Asn Gly 355 360 365 Met Glu Asp Ala Gly Asp Thr Glu GluPhe Gln Ser Asp Pro Lys Pro 370 375 380 Ser Gln Tyr Arg Lys Pro Ser LeuPhe His Gln Ser Thr Ser Ser Pro 385 390 395 400 Tyr Val Ser Lys Ser GluThr His Gln Pro Met Thr Ser Gly Ser Phe 405 410 415 Pro Ile Asn Gly LeuHis Ser His Ser Glu Val Leu Thr Ala Arg Pro 420 425 430 Gln Ser Met GluAsn Ser Pro Thr Ile Asn Glu Pro Lys Asp Lys Ser 435 440 445 Ser Glu LeuThr Arg Leu Glu Ser Val Leu Pro Arg Ser Pro Ala Asp 450 455 460 Glu LeuSer His Cys Val Glu Pro Glu Pro Ser Gln Val Pro Gly Gly 465 470 475 480Ser Ser Arg Asp Arg Gln Gln Gly Ser Glu Glu Glu Pro Ser Pro Val 485 490495 Leu Lys Thr Leu Glu Arg Ser Ala Ala Arg Lys Met Pro Ser Lys Ser 500505 510 Leu Glu Asp Ile Ser Ser Asp Ser Ser Asn Gln Ala Lys Val Asp Asn515 520 525 Gln Pro Glu Glu Leu Val Arg Ser Ala Glu Asp Asp Glu Lys ProAsp 530 535 540 Gln Lys Pro Val Thr Asn Glu Cys Val Pro Arg Ile Ser ThrVal Pro 545 550 555 560 Thr Gln Pro Asp Asn Pro Phe Ser His Pro Asp LysLeu Lys Arg Met 565 570 575 Ser Lys Ser Val Pro Ala Phe Leu Gln Asp GluAla Asp Asp Arg Glu 580 585 590 Thr Asp Thr Ala Ser Glu Ser Ser Tyr GlnLeu Ser Arg His Lys Lys 595 600 605 Ser Pro Ser Ser Leu Thr Asn Leu SerSer Ser Ser Gly Met Thr Ser 610 615 620 Leu Ser Ser Val Ser Gly Ser ValMet Ser Val Tyr Ser Gly Asp Phe 625 630 635 640 Gly Asn Leu Glu Val LysGly Asn Ile Gln Phe Ala Ile Glu Tyr Val 645 650 655 Glu Ser Leu Lys GluLeu His Val Phe Val Ala Gln Cys Lys Asp Leu 660 665 670 Ala Ala Ala AspVal Lys Lys Gln Arg Ser Asp Pro Tyr Val Lys Ala 675 680 685 Tyr Leu LeuPro Asp Lys Gly Lys Met Gly Lys Lys Lys Thr Leu Val 690 695 700 Val LysLys Thr Leu Asn Pro Val Tyr Asn Glu Ile Leu Arg Tyr Lys 705 710 715 720Ile Glu Lys Gln Ile Leu Lys Thr Gln Lys Leu Asn Leu Ser Ile Trp 725 730735 His Arg Asp Thr Phe Lys Arg Asn Ser Phe Leu Gly Glu Val Glu Leu 740745 750 Asp Leu Glu Thr Trp Asp Trp Asp Asn Lys Gln Asn Lys Gln Leu Arg755 760 765 Trp Tyr Pro Leu Lys Arg Lys Thr Ala Pro Val Ala Leu Glu AlaGlu 770 775 780 Asn Arg Gly Glu Met Lys Leu Ala Leu Gln Tyr Val Pro GluPro Val 785 790 795 800 Pro Gly Lys Lys Leu Pro Thr Thr Gly Glu Val HisIle Trp Val Lys 805 810 815 Glu Cys Leu Asp Leu Pro Leu Leu Arg Gly SerHis Leu Asn Ser Phe 820 825 830 Val Lys Cys Thr Ile Leu Pro Asp Thr SerArg Lys Ser Arg Gln Lys 835 840 845 Thr Arg Ala Val Gly Lys Thr Thr AsnPro Ile Phe Asn His Thr Met 850 855 860 Val Tyr Asp Gly Phe Arg Pro GluAsp Leu Met Glu Ala Cys Val Glu 865 870 875 880 Leu Thr Val Trp Asp HisTyr Lys Leu Thr Asn Gln Phe Leu Gly Gly 885 890 895 Leu Arg Ile Gly PheGly Thr Gly Lys Ser Tyr Gly Thr Glu Val Asp 900 905 910 Trp Met Asp SerThr Ser Glu Glu Val Ala Leu Trp Glu Lys Met Val 915 920 925 Asn Ser ProAsn Thr Trp Ile Glu Ala Thr Leu Pro Leu Arg Met Leu 930 935 940 Leu IleAla Lys Ile Ser Lys 945 950 55 2478 DNA Homo sapiens CDS (144)..(2156)55 actagtaaaa aaagaaaaag aaaaaataaa gtgaaagagg cgtgttgtct agtttcaaag 60gagaggagag aaggcaactc tggtagctct ccttgtctgg ttgttttgaa gaaagaagag 120tagaagaaaa agttgagtaa atc atg tcg gag tta ctg gac ctt tct ttt ctg 173Met Ser Glu Leu Leu Asp Leu Ser Phe Leu 1 5 10 tct gag gag gaa aag gatttg att ctc agt gtt cta cag cga gat gaa 221 Ser Glu Glu Glu Lys Asp LeuIle Leu Ser Val Leu Gln Arg Asp Glu 15 20 25 gag gtc cgg aaa gca gat gagaaa agg att agg cga cta aag aat gag 269 Glu Val Arg Lys Ala Asp Glu LysArg Ile Arg Arg Leu Lys Asn Glu 30 35 40 tta ctg gag ata aaa agg aaa ggggcc aag agg ggc agc caa cac tac 317 Leu Leu Glu Ile Lys Arg Lys Gly AlaLys Arg Gly Ser Gln His Tyr 45 50 55 agt gat cgg acc tgt gcc cgg tgc caggag agc ctg ggc cgt ttg agt 365 Ser Asp Arg Thr Cys Ala Arg Cys Gln GluSer Leu Gly Arg Leu Ser 60 65 70 ccc aaa acc aat act tgt cgg ggt tgt aatcac ctg gtg tgt cgg gac 413 Pro Lys Thr Asn Thr Cys Arg Gly Cys Asn HisLeu Val Cys Arg Asp 75 80 85 90 tgc cgc ata cag gaa agc aat ggt acc tggagg tgc aag gtg tgc gcc 461 Cys Arg Ile Gln Glu Ser Asn Gly Thr Trp ArgCys Lys Val Cys Ala 95 100 105 aag gaa ata gag ttg aag aaa gca act ggggac tgg ttt tat gac cag 509 Lys Glu Ile Glu Leu Lys Lys Ala Thr Gly AspTrp Phe Tyr Asp Gln 110 115 120 aaa gtg aat cgc ttt gct tac cgc aca ggtagt gag ata atc agg atg 557 Lys Val Asn Arg Phe Ala Tyr Arg Thr Gly SerGlu Ile Ile Arg Met 125 130 135 tcc ctg cgc cac aaa cct gca gtg agt aaaaga gag aca gtg gga cag 605 Ser Leu Arg His Lys Pro Ala Val Ser Lys ArgGlu Thr Val Gly Gln 140 145 150 tcc ctc ctt cat cag aca cag atg ggt gacatc tgg cca gga aga aag 653 Ser Leu Leu His Gln Thr Gln Met Gly Asp IleTrp Pro Gly Arg Lys 155 160 165 170 atc att cag gag cgg cag aag gag cccagt gtg cta ttt gaa gtg cca 701 Ile Ile Gln Glu Arg Gln Lys Glu Pro SerVal Leu Phe Glu Val Pro 175 180 185 aag ctg aaa agt gga aag agt gca ttggaa gct gag agt gag agt ctg 749 Lys Leu Lys Ser Gly Lys Ser Ala Leu GluAla Glu Ser Glu Ser Leu 190 195 200 gat agc ttc aca gct gac tcg gat agcacc tcc agg aga gac tct ctg 797 Asp Ser Phe Thr Ala Asp Ser Asp Ser ThrSer Arg Arg Asp Ser Leu 205 210 215 gat aaa tct ggc ctc ttt cca gaa tggaag aag atg tct gct ccc aaa 845 Asp Lys Ser Gly Leu Phe Pro Glu Trp LysLys Met Ser Ala Pro Lys 220 225 230 tct caa gta gaa aag gaa act cag cctgga ggt caa aat gtg gta ttt 893 Ser Gln Val Glu Lys Glu Thr Gln Pro GlyGly Gln Asn Val Val Phe 235 240 245 250 gtg gat gag ggt gag atg ata tttaag aag aac acc aga aaa atc ctc 941 Val Asp Glu Gly Glu Met Ile Phe LysLys Asn Thr Arg Lys Ile Leu 255 260 265 agg cct tca gag tac act aaa tctgtg ata gat ctt cgc cca gaa gat 989 Arg Pro Ser Glu Tyr Thr Lys Ser ValIle Asp Leu Arg Pro Glu Asp 270 275 280 gtg gta cat gaa agt ggc tcc ttggga gac aga agc aaa tcc gtc cca 1037 Val Val His Glu Ser Gly Ser Leu GlyAsp Arg Ser Lys Ser Val Pro 285 290 295 ggc ctc aat gtg gat atg gaa gaggaa gaa gaa gaa gaa gac att gac 1085 Gly Leu Asn Val Asp Met Glu Glu GluGlu Glu Glu Glu Asp Ile Asp 300 305 310 cac cta gtg aag tta cat cgc cagaag cta gcc aga agc agc atg caa 1133 His Leu Val Lys Leu His Arg Gln LysLeu Ala Arg Ser Ser Met Gln 315 320 325 330 agt ggc tcc tcc atg agt acgatc ggc agc atg atg agc atc tac agt 1181 Ser Gly Ser Ser Met Ser Thr IleGly Ser Met Met Ser Ile Tyr Ser 335 340 345 gaa gct ggt gat ttc ggg aacatc ttt gtg act ggc agg att gcc ttt 1229 Glu Ala Gly Asp Phe Gly Asn IlePhe Val Thr Gly Arg Ile Ala Phe 350 355 360 tcc ctg aag tat gag cag caaacc cag agt ctg gtt gtc cat gtg aag 1277 Ser Leu Lys Tyr Glu Gln Gln ThrGln Ser Leu Val Val His Val Lys 365 370 375 gag tgc cat cag ctg gcc tatgct gat gaa gcc aag aag cgc tct aac 1325 Glu Cys His Gln Leu Ala Tyr AlaAsp Glu Ala Lys Lys Arg Ser Asn 380 385 390 cca tat gtg aag act tac cttctg cct gac aag tcc cgc caa gga aaa 1373 Pro Tyr Val Lys Thr Tyr Leu LeuPro Asp Lys Ser Arg Gln Gly Lys 395 400 405 410 aga aaa acc agc atc aagcgg gac act att aat cca cta tat gat gag 1421 Arg Lys Thr Ser Ile Lys ArgAsp Thr Ile Asn Pro Leu Tyr Asp Glu 415 420 425 acg ctg agg tat gag atccca gaa tct ctc ctg gcc cag agg acc ctg 1469 Thr Leu Arg Tyr Glu Ile ProGlu Ser Leu Leu Ala Gln Arg Thr Leu 430 435 440 cag ttc tca gtt tgg catcat ggt cgt ttt ggc aga aac act ttc ctt 1517 Gln Phe Ser Val Trp His HisGly Arg Phe Gly Arg Asn Thr Phe Leu 445 450 455 gga gag gca gag atc cagatg gat tcc tgg aag ctt gat aag aaa ctg 1565 Gly Glu Ala Glu Ile Gln MetAsp Ser Trp Lys Leu Asp Lys Lys Leu 460 465 470 gat cat tgc ctc cct ttacat gga aag atc agt gct gag tcc ccg act 1613 Asp His Cys Leu Pro Leu HisGly Lys Ile Ser Ala Glu Ser Pro Thr 475 480 485 490 ggc ttg cca tca cacaaa ggc gag ttg gtg gtt tca ttg aaa tac atc 1661 Gly Leu Pro Ser His LysGly Glu Leu Val Val Ser Leu Lys Tyr Ile 495 500 505 cca gcc tcc aaa acccct gtt gga ggt gac cgg aaa aag agt aaa ggt 1709 Pro Ala Ser Lys Thr ProVal Gly Gly Asp Arg Lys Lys Ser Lys Gly 510 515 520 ggg gaa ggg gga gagctc cag gtg tgg atc aaa gaa gcc aag aac ttg 1757 Gly Glu Gly Gly Glu LeuGln Val Trp Ile Lys Glu Ala Lys Asn Leu 525 530 535 acg gct gcc aaa gcagga ggg act tca gac agc ttt gtc aag gga tac 1805 Thr Ala Ala Lys Ala GlyGly Thr Ser Asp Ser Phe Val Lys Gly Tyr 540 545 550 ctc ctt ccc atg aggaac aag gcc agt aaa cgt aaa act cct gtg atg 1853 Leu Leu Pro Met Arg AsnLys Ala Ser Lys Arg Lys Thr Pro Val Met 555 560 565 570 aag aag acc ctgaat cct cac tac aac cat aca ttt gtc tac aat ggt 1901 Lys Lys Thr Leu AsnPro His Tyr Asn His Thr Phe Val Tyr Asn Gly 575 580 585 gtg agg ctg gaagat cta cag cat atg tgc ctg gaa ctg act gtg tgg 1949 Val Arg Leu Glu AspLeu Gln His Met Cys Leu Glu Leu Thr Val Trp 590 595 600 gac cgg gag cccctg gcc agc aat gac ttc ctg gga ggg gtc agg ctg 1997 Asp Arg Glu Pro LeuAla Ser Asn Asp Phe Leu Gly Gly Val Arg Leu 605 610 615 ggt gtt ggc actggg atc agt aat ggg gaa gtg gtg gac tgg atg gac 2045 Gly Val Gly Thr GlyIle Ser Asn Gly Glu Val Val Asp Trp Met Asp 620 625 630 tcg act ggg gaagaa gtg agc ctg tgg cag aag atg cga cag tac cca 2093 Ser Thr Gly Glu GluVal Ser Leu Trp Gln Lys Met Arg Gln Tyr Pro 635 640 645 650 ggg tct tgggca gaa ggg act ctg cag ctc cgt tcc tca atg gcc aag 2141 Gly Ser Trp AlaGlu Gly Thr Leu Gln Leu Arg Ser Ser Met Ala Lys 655 660 665 cag aag ctgggt tta tgagtccctg tcctcttctg caggtccagc cctggcgagg 2196 Gln Lys Leu GlyLeu 670 gcaggtcaga ggaagtgaag aaatcaagag caaagattta taatttaatgtgtatgtgtg 2256 tatgtgtgta tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tacaaacatgtattttctgc 2316 aaatctcatt atgctggcta gagtgatgca gacttgttct tctttttaaagcagtctcaa 2376 gaataagcat ttctttaaaa tgtttctgtg tataatctag tttattttcagagtccattt 2436 tttcttatgt ctttataagg ttcacttaac ttaaaaacag ct 2478 56671 PRT Homo sapiens 56 Met Ser Glu Leu Leu Asp Leu Ser Phe Leu Ser GluGlu Glu Lys Asp 1 5 10 15 Leu Ile Leu Ser Val Leu Gln Arg Asp Glu GluVal Arg Lys Ala Asp 20 25 30 Glu Lys Arg Ile Arg Arg Leu Lys Asn Glu LeuLeu Glu Ile Lys Arg 35 40 45 Lys Gly Ala Lys Arg Gly Ser Gln His Tyr SerAsp Arg Thr Cys Ala 50 55 60 Arg Cys Gln Glu Ser Leu Gly Arg Leu Ser ProLys Thr Asn Thr Cys 65 70 75 80 Arg Gly Cys Asn His Leu Val Cys Arg AspCys Arg Ile Gln Glu Ser 85 90 95 Asn Gly Thr Trp Arg Cys Lys Val Cys AlaLys Glu Ile Glu Leu Lys 100 105 110 Lys Ala Thr Gly Asp Trp Phe Tyr AspGln Lys Val Asn Arg Phe Ala 115 120 125 Tyr Arg Thr Gly Ser Glu Ile IleArg Met Ser Leu Arg His Lys Pro 130 135 140 Ala Val Ser Lys Arg Glu ThrVal Gly Gln Ser Leu Leu His Gln Thr 145 150 155 160 Gln Met Gly Asp IleTrp Pro Gly Arg Lys Ile Ile Gln Glu Arg Gln 165 170 175 Lys Glu Pro SerVal Leu Phe Glu Val Pro Lys Leu Lys Ser Gly Lys 180 185 190 Ser Ala LeuGlu Ala Glu Ser Glu Ser Leu Asp Ser Phe Thr Ala Asp 195 200 205 Ser AspSer Thr Ser Arg Arg Asp Ser Leu Asp Lys Ser Gly Leu Phe 210 215 220 ProGlu Trp Lys Lys Met Ser Ala Pro Lys Ser Gln Val Glu Lys Glu 225 230 235240 Thr Gln Pro Gly Gly Gln Asn Val Val Phe Val Asp Glu Gly Glu Met 245250 255 Ile Phe Lys Lys Asn Thr Arg Lys Ile Leu Arg Pro Ser Glu Tyr Thr260 265 270 Lys Ser Val Ile Asp Leu Arg Pro Glu Asp Val Val His Glu SerGly 275 280 285 Ser Leu Gly Asp Arg Ser Lys Ser Val Pro Gly Leu Asn ValAsp Met 290 295 300 Glu Glu Glu Glu Glu Glu Glu Asp Ile Asp His Leu ValLys Leu His 305 310 315 320 Arg Gln Lys Leu Ala Arg Ser Ser Met Gln SerGly Ser Ser Met Ser 325 330 335 Thr Ile Gly Ser Met Met Ser Ile Tyr SerGlu Ala Gly Asp Phe Gly 340 345 350 Asn Ile Phe Val Thr Gly Arg Ile AlaPhe Ser Leu Lys Tyr Glu Gln 355 360 365 Gln Thr Gln Ser Leu Val Val HisVal Lys Glu Cys His Gln Leu Ala 370 375 380 Tyr Ala Asp Glu Ala Lys LysArg Ser Asn Pro Tyr Val Lys Thr Tyr 385 390 395 400 Leu Leu Pro Asp LysSer Arg Gln Gly Lys Arg Lys Thr Ser Ile Lys 405 410 415 Arg Asp Thr IleAsn Pro Leu Tyr Asp Glu Thr Leu Arg Tyr Glu Ile 420 425 430 Pro Glu SerLeu Leu Ala Gln Arg Thr Leu Gln Phe Ser Val Trp His 435 440 445 His GlyArg Phe Gly Arg Asn Thr Phe Leu Gly Glu Ala Glu Ile Gln 450 455 460 MetAsp Ser Trp Lys Leu Asp Lys Lys Leu Asp His Cys Leu Pro Leu 465 470 475480 His Gly Lys Ile Ser Ala Glu Ser Pro Thr Gly Leu Pro Ser His Lys 485490 495 Gly Glu Leu Val Val Ser Leu Lys Tyr Ile Pro Ala Ser Lys Thr Pro500 505 510 Val Gly Gly Asp Arg Lys Lys Ser Lys Gly Gly Glu Gly Gly GluLeu 515 520 525 Gln Val Trp Ile Lys Glu Ala Lys Asn Leu Thr Ala Ala LysAla Gly 530 535 540 Gly Thr Ser Asp Ser Phe Val Lys Gly Tyr Leu Leu ProMet Arg Asn 545 550 555 560 Lys Ala Ser Lys Arg Lys Thr Pro Val Met LysLys Thr Leu Asn Pro 565 570 575 His Tyr Asn His Thr Phe Val Tyr Asn GlyVal Arg Leu Glu Asp Leu 580 585 590 Gln His Met Cys Leu Glu Leu Thr ValTrp Asp Arg Glu Pro Leu Ala 595 600 605 Ser Asn Asp Phe Leu Gly Gly ValArg Leu Gly Val Gly Thr Gly Ile 610 615 620 Ser Asn Gly Glu Val Val AspTrp Met Asp Ser Thr Gly Glu Glu Val 625 630 635 640 Ser Leu Trp Gln LysMet Arg Gln Tyr Pro Gly Ser Trp Ala Glu Gly 645 650 655 Thr Leu Gln LeuArg Ser Ser Met Ala Lys Gln Lys Leu Gly Leu 660 665 670 57 5993 DNA Homosapiens CDS (73)..(5859) 57 gagcgcgccg tcctcgagtc cccgagccgc ggagcccgcccgcgcccctc gggccgcccc 60 gcgtccctcg cc atg gcg cgg ctc gcg gac tac ttcgtg ctg gtg gcg ttc 111 Met Ala Arg Leu Ala Asp Tyr Phe Val Leu Val AlaPhe 1 5 10 ggg ccg cac ccg cgc ggg agt ggg gaa ggc cag ggc cag att ctgcag 159 Gly Pro His Pro Arg Gly Ser Gly Glu Gly Gln Gly Gln Ile Leu Gln15 20 25 cgc ttc cca gag aag gac tgg gag gac aac cca ttc ccc cag ggc atc207 Arg Phe Pro Glu Lys Asp Trp Glu Asp Asn Pro Phe Pro Gln Gly Ile 3035 40 45 gag ctg ttt tgc cag ccc agc ggg tgg cag ctg tgt ccc gag agg aat255 Glu Leu Phe Cys Gln Pro Ser Gly Trp Gln Leu Cys Pro Glu Arg Asn 5055 60 cca ccg acc ttc ttt gtt gct gtc ctc acc gac atc aac tcc gag cgc303 Pro Pro Thr Phe Phe Val Ala Val Leu Thr Asp Ile Asn Ser Glu Arg 6570 75 cac tac tgc gcc tgc ttg acc ttc tgg gag cca gcg gag cct tca cag351 His Tyr Cys Ala Cys Leu Thr Phe Trp Glu Pro Ala Glu Pro Ser Gln 8085 90 gaa acg acg cgc gtg gag gat gcc aca gag agg gag gaa gag ggg gat399 Glu Thr Thr Arg Val Glu Asp Ala Thr Glu Arg Glu Glu Glu Gly Asp 95100 105 gag gga ggc cag acc cac ctg tct ccc aca gca cct gcc cca tct gcc447 Glu Gly Gly Gln Thr His Leu Ser Pro Thr Ala Pro Ala Pro Ser Ala 110115 120 125 cag ctg ttt gca ccg aag acg ctg gta ctg gtg tcg cga ctc gaccac 495 Gln Leu Phe Ala Pro Lys Thr Leu Val Leu Val Ser Arg Leu Asp His130 135 140 acg gag gtg ttc agg aac agc ctt ggc ctc atc tat gcc atc cacgtg 543 Thr Glu Val Phe Arg Asn Ser Leu Gly Leu Ile Tyr Ala Ile His Val145 150 155 gag ggc ctg aat gtg tgc ctg gag aac gtg att ggg aac ctg ctgacg 591 Glu Gly Leu Asn Val Cys Leu Glu Asn Val Ile Gly Asn Leu Leu Thr160 165 170 tgc act gtg ccc ctg gct ggg ggc tcg cag agg acg atc tct ttgggg 639 Cys Thr Val Pro Leu Ala Gly Gly Ser Gln Arg Thr Ile Ser Leu Gly175 180 185 gct ggt gac cgg cag gtc atc cag act cca ctg gcc gac tcg ctgccc 687 Ala Gly Asp Arg Gln Val Ile Gln Thr Pro Leu Ala Asp Ser Leu Pro190 195 200 205 gtc agc cgc tgc agc gtg gcc ctg ctc ttc cgc cag cta ggcatc acc 735 Val Ser Arg Cys Ser Val Ala Leu Leu Phe Arg Gln Leu Gly IleThr 210 215 220 aac gtg ctg tct ttg ttc tgt gcc gcc ctc acg gag cac aaggtt ctc 783 Asn Val Leu Ser Leu Phe Cys Ala Ala Leu Thr Glu His Lys ValLeu 225 230 235 ttc ctg tcc cgg agc tac cag cgg ctc gcc gat gcc tgt aggggc ctc 831 Phe Leu Ser Arg Ser Tyr Gln Arg Leu Ala Asp Ala Cys Arg GlyLeu 240 245 250 ctg gca ctg ctg ttt cct ctc aga tac agc ttc acc tat gtgccc atc 879 Leu Ala Leu Leu Phe Pro Leu Arg Tyr Ser Phe Thr Tyr Val ProIle 255 260 265 ctg ccg gct cag ctg ctg gag gtc ctc agc aca ccc acg cccttc atc 927 Leu Pro Ala Gln Leu Leu Glu Val Leu Ser Thr Pro Thr Pro PheIle 270 275 280 285 att ggg gtc aac gcg gcc ttc cag gca gag acc cag gagctg ctc gat 975 Ile Gly Val Asn Ala Ala Phe Gln Ala Glu Thr Gln Glu LeuLeu Asp 290 295 300 gtg att gtt gct gat ctg gat gga ggg acg gtc acc attcct gag tgt 1023 Val Ile Val Ala Asp Leu Asp Gly Gly Thr Val Thr Ile ProGlu Cys 305 310 315 gtg cac att cca ccc ttg cca gag cca ctg cag agt cagacg cac agt 1071 Val His Ile Pro Pro Leu Pro Glu Pro Leu Gln Ser Gln ThrHis Ser 320 325 330 gtg ctg agc atg gtc ctg gac ccg gag ctg gag ttg gctgac ctc gcc 1119 Val Leu Ser Met Val Leu Asp Pro Glu Leu Glu Leu Ala AspLeu Ala 335 340 345 ttc cct ccg ccc acg aca tcc acc tcc tcc ctg aag atgcag gac aag 1167 Phe Pro Pro Pro Thr Thr Ser Thr Ser Ser Leu Lys Met GlnAsp Lys 350 355 360 365 gag ctg cgc gcg gtc ttc ctg cgg ctg ttc gct cagctg ctg cag ggc 1215 Glu Leu Arg Ala Val Phe Leu Arg Leu Phe Ala Gln LeuLeu Gln Gly 370 375 380 tat cgc tgg tgc ctg cac gtc gtg cgc atc cac ccggag cct gtc atc 1263 Tyr Arg Trp Cys Leu His Val Val Arg Ile His Pro GluPro Val Ile 385 390 395 cgc ttc cat aag gca gcc ttc ctg ggg cag cgt gggctg gta gag gac 1311 Arg Phe His Lys Ala Ala Phe Leu Gly Gln Arg Gly LeuVal Glu Asp 400 405 410 gat ttc ctg atg aag gtg ctg gag ggc atg gcc tttgct ggc ttt gtg 1359 Asp Phe Leu Met Lys Val Leu Glu Gly Met Ala Phe AlaGly Phe Val 415 420 425 tca gag cgt ggg gtc cca tac cgc cct acg gac ctgttc gat gag ctg 1407 Ser Glu Arg Gly Val Pro Tyr Arg Pro Thr Asp Leu PheAsp Glu Leu 430 435 440 445 gtg gcc cac gag gtg gca agg atg cgg gcg gatgag aac cac ccc cag 1455 Val Ala His Glu Val Ala Arg Met Arg Ala Asp GluAsn His Pro Gln 450 455 460 cgt gtc ctg cgt cac gtc cag gaa ctg gca gagcag ctc tac aag aac 1503 Arg Val Leu Arg His Val Gln Glu Leu Ala Glu GlnLeu Tyr Lys Asn 465 470 475 gag aac ccg tac cca gcc gtg gcg atg cac aaggta cag agg ccc ggt 1551 Glu Asn Pro Tyr Pro Ala Val Ala Met His Lys ValGln Arg Pro Gly 480 485 490 gag agc agc cac ctg cga cgg gtg ccc cga cccttc ccc cgg ctg gat 1599 Glu Ser Ser His Leu Arg Arg Val Pro Arg Pro PhePro Arg Leu Asp 495 500 505 gag ggc acc gtg cag tgg atc gtg gac cag gctgca gcc aag atg cag 1647 Glu Gly Thr Val Gln Trp Ile Val Asp Gln Ala AlaAla Lys Met Gln 510 515 520 525 ggt gca ccc cca gct gtg aag gcc gag aggagg acc acc gtg ccc tca 1695 Gly Ala Pro Pro Ala Val Lys Ala Glu Arg ArgThr Thr Val Pro Ser 530 535 540 ggg ccc ccc atg act gcc ata ctg gag cggtgc agt ggg ctg cat gtc 1743 Gly Pro Pro Met Thr Ala Ile Leu Glu Arg CysSer Gly Leu His Val 545 550 555 aac agc gcc cgg cgg ctg gag gtt gtg cgcaac tgc atc tcc tac gtg 1791 Asn Ser Ala Arg Arg Leu Glu Val Val Arg AsnCys Ile Ser Tyr Val 560 565 570 ttt gag ggg aaa atg ctt gag gcc aag aagctg ctc cca gcc gtg ttg 1839 Phe Glu Gly Lys Met Leu Glu Ala Lys Lys LeuLeu Pro Ala Val Leu 575 580 585 agg gcc ctg aag ggg cga gtt gcc cgc cgctgc ctc gcc cag gag ctg 1887 Arg Ala Leu Lys Gly Arg Val Ala Arg Arg CysLeu Ala Gln Glu Leu 590 595 600 605 cac ctg cat gtg cag cag aac cgt gcggtc ctg gac cac cag cag ttt 1935 His Leu His Val Gln Gln Asn Arg Ala ValLeu Asp His Gln Gln Phe 610 615 620 gac ttt gtc gtc cgt atg atg aac tgctgc ctg cag gac tgc act tct 1983 Asp Phe Val Val Arg Met Met Asn Cys CysLeu Gln Asp Cys Thr Ser 625 630 635 ctg gac gag cat ggc att gcg gcg gctctg ctg cct ctg gtc aca gcc 2031 Leu Asp Glu His Gly Ile Ala Ala Ala LeuLeu Pro Leu Val Thr Ala 640 645 650 ttc tgc cgg aag ctg agc ccg ggg gtgacg cag ttt gca tac agc tgt 2079 Phe Cys Arg Lys Leu Ser Pro Gly Val ThrGln Phe Ala Tyr Ser Cys 655 660 665 gtg cag gag cac gtg gtg tgg agc acgcca cag ttc tgg gag gcc atg 2127 Val Gln Glu His Val Val Trp Ser Thr ProGln Phe Trp Glu Ala Met 670 675 680 685 ttc tat ggg gat gtg cag act cacatc cgg gcc ctc tac ctg gag ccc 2175 Phe Tyr Gly Asp Val Gln Thr His IleArg Ala Leu Tyr Leu Glu Pro 690 695 700 acg gag gac ctg gcc ccc gcc caggag gtt ggg gag gca cct tcc cag 2223 Thr Glu Asp Leu Ala Pro Ala Gln GluVal Gly Glu Ala Pro Ser Gln 705 710 715 gag gac gag cgc tct gcc cta gacgtg gct tct gag cag cgg cgc ttg 2271 Glu Asp Glu Arg Ser Ala Leu Asp ValAla Ser Glu Gln Arg Arg Leu 720 725 730 tgg cca act ctg agt cgt gag aagcag cag gag ctg gtg cag aag gag 2319 Trp Pro Thr Leu Ser Arg Glu Lys GlnGln Glu Leu Val Gln Lys Glu 735 740 745 gag agc acg gtg ttc agc cag gccatc cac tat gcc aac cgc atg agc 2367 Glu Ser Thr Val Phe Ser Gln Ala IleHis Tyr Ala Asn Arg Met Ser 750 755 760 765 tac ctc ctc ctg ccc ctg gacagc agc aag agc cgc cta ctt cgg gag 2415 Tyr Leu Leu Leu Pro Leu Asp SerSer Lys Ser Arg Leu Leu Arg Glu 770 775 780 cgt gcc ggg ctg ggc gac ctggag agc gcc agc aac agc ctg gtc acc 2463 Arg Ala Gly Leu Gly Asp Leu GluSer Ala Ser Asn Ser Leu Val Thr 785 790 795 aac agc atg gct ggc agt gtggcc gag agc tat gac acg gag agc ggc 2511 Asn Ser Met Ala Gly Ser Val AlaGlu Ser Tyr Asp Thr Glu Ser Gly 800 805 810 ttc gag gat gca gag acc tgcgac gta gct ggg gct gtg gtc cgc ttc 2559 Phe Glu Asp Ala Glu Thr Cys AspVal Ala Gly Ala Val Val Arg Phe 815 820 825 atc aac cgc ttt gtg gac aaggtc tgc acg gag agt ggg gtc acc agc 2607 Ile Asn Arg Phe Val Asp Lys ValCys Thr Glu Ser Gly Val Thr Ser 830 835 840 845 gac cac ctc aag ggg ctgcat gtc atg gtg cca gac att gtc cag atg 2655 Asp His Leu Lys Gly Leu HisVal Met Val Pro Asp Ile Val Gln Met 850 855 860 cac atc gag acc ctg gaggcc gtg cag cgg gag agc cgg agg ctg ccg 2703 His Ile Glu Thr Leu Glu AlaVal Gln Arg Glu Ser Arg Arg Leu Pro 865 870 875 ccc atc cag aag ccc aagctg ctg cgg ccg cgc ctg ctg ccg ggt gag 2751 Pro Ile Gln Lys Pro Lys LeuLeu Arg Pro Arg Leu Leu Pro Gly Glu 880 885 890 gag tgt gtg ctg gac ggcctg cgc gtc tac ctg ctg ccg gat ggg cgt 2799 Glu Cys Val Leu Asp Gly LeuArg Val Tyr Leu Leu Pro Asp Gly Arg 895 900 905 gag gag ggc gcg ggg ggcagt gct ggg gga cca gca ttg ctc cca gct 2847 Glu Glu Gly Ala Gly Gly SerAla Gly Gly Pro Ala Leu Leu Pro Ala 910 915 920 925 gag ggc gcc gtc ttcctc acc acg tac cgg gtc atc ttc acg ggg atg 2895 Glu Gly Ala Val Phe LeuThr Thr Tyr Arg Val Ile Phe Thr Gly Met 930 935 940 ccc acg gac ccc ctggtt ggg gag cag gtg gtg gtc cgc tcc ttc ccg 2943 Pro Thr Asp Pro Leu ValGly Glu Gln Val Val Val Arg Ser Phe Pro 945 950 955 gtg gct gcg ctg accaag gag aag cgc atc agc gtc cag acc cct gtg 2991 Val Ala Ala Leu Thr LysGlu Lys Arg Ile Ser Val Gln Thr Pro Val 960 965 970 gac cag ctc ctg caggac ggg ctc cag ctg cgc tcc tgc aca ttc cag 3039 Asp Gln Leu Leu Gln AspGly Leu Gln Leu Arg Ser Cys Thr Phe Gln 975 980 985 ctg ctg aaa atg gccttt gac gag gag gtg ggg tct gac agc gcc gag 3087 Leu Leu Lys Met Ala PheAsp Glu Glu Val Gly Ser Asp Ser Ala Glu 990 995 1000 1005 ctc ttc cgtaag cag ctg cat aag ctg cgg tac ccg ccg gac atc agg 3135 Leu Phe Arg LysGln Leu His Lys Leu Arg Tyr Pro Pro Asp Ile Arg 1010 1015 1020 gcc accttt gcg ttc acc ttg ggc tct gcc cac aca cct ggc cgg cca 3183 Ala Thr PheAla Phe Thr Leu Gly Ser Ala His Thr Pro Gly Arg Pro 1025 1030 1035 ccgcga gtc acc aag gac aag ggt cct tcc ctc aga acc ctg tcc cgg 3231 Pro ArgVal Thr Lys Asp Lys Gly Pro Ser Leu Arg Thr Leu Ser Arg 1040 1045 1050aac ctg gtc aag aac gcc aag aag acc atc ggg cgg cag cat gtc act 3279 AsnLeu Val Lys Asn Ala Lys Lys Thr Ile Gly Arg Gln His Val Thr 1055 10601065 cgc aag aag tac aac ccc ccc agc tgg gag cac cgg ggc cag ccg ccc3327 Arg Lys Lys Tyr Asn Pro Pro Ser Trp Glu His Arg Gly Gln Pro Pro1070 1075 1080 1085 cct gag gac cag gag gac gag atc tca gtg tcg gag gagctg gag ccc 3375 Pro Glu Asp Gln Glu Asp Glu Ile Ser Val Ser Glu Glu LeuGlu Pro 1090 1095 1100 agc acg ctg acc ccg tcc tca gcc ctg aag ccc tccgac cgc atg acc 3423 Ser Thr Leu Thr Pro Ser Ser Ala Leu Lys Pro Ser AspArg Met Thr 1105 1110 1115 atg agc agc ctg gtg gaa agg gct tgc tgt cgcgac tac cag cgc ctc 3471 Met Ser Ser Leu Val Glu Arg Ala Cys Cys Arg AspTyr Gln Arg Leu 1120 1125 1130 ggt ctg ggc acc ctg agc agc agc ctg agccgg gcc aag tct gag ccc 3519 Gly Leu Gly Thr Leu Ser Ser Ser Leu Ser ArgAla Lys Ser Glu Pro 1135 1140 1145 ttc cgc att tct ccg gtc aac cgc atgtat gcc atc tgc cgc agc tac 3567 Phe Arg Ile Ser Pro Val Asn Arg Met TyrAla Ile Cys Arg Ser Tyr 1150 1155 1160 1165 cca ggg ctg ctg atc gtg cgccag agt gtc cag gac aac gcc ctg cag 3615 Pro Gly Leu Leu Ile Val Arg GlnSer Val Gln Asp Asn Ala Leu Gln 1170 1175 1180 cgc gtg tcc cgc tgc taccgc cag aac cgc ttc ccc gtg gtc tgc tgg 3663 Arg Val Ser Arg Cys Tyr ArgGln Asn Arg Phe Pro Val Val Cys Trp 1185 1190 1195 cgc agc ggg cgg tccaag gcg gtg ctg ctg cgc tct gga ggc ctg cat 3711 Arg Ser Gly Arg Ser LysAla Val Leu Leu Arg Ser Gly Gly Leu His 1200 1205 1210 ggc aaa ggt gtcgtc ggc ctc ttc aag gcc cag aac gca cct tct cca 3759 Gly Lys Gly Val ValGly Leu Phe Lys Ala Gln Asn Ala Pro Ser Pro 1215 1220 1225 ggc cag tcccag gcg gac tcg agt agc ctg gag cag gag aag tac ctg 3807 Gly Gln Ser GlnAla Asp Ser Ser Ser Leu Glu Gln Glu Lys Tyr Leu 1230 1235 1240 1245 caggct gtg gtc agc tcc atg ccc cgc tac gcc gac gcg tcg gga cgc 3855 Gln AlaVal Val Ser Ser Met Pro Arg Tyr Ala Asp Ala Ser Gly Arg 1250 1255 1260aac acg ctt agc ggc ttc tcc tca gcc cac atg ggc agt cac ggt aag 3903 AsnThr Leu Ser Gly Phe Ser Ser Ala His Met Gly Ser His Gly Lys 1265 12701275 tgg ggc agt gtc cgg acc agt gga cgc agc agt ggc ctt ggc acc gat3951 Trp Gly Ser Val Arg Thr Ser Gly Arg Ser Ser Gly Leu Gly Thr Asp1280 1285 1290 gtg ggc tcc cgg cta gct ggc aga gac gcg ctg gcc cca ccccag gcc 3999 Val Gly Ser Arg Leu Ala Gly Arg Asp Ala Leu Ala Pro Pro GlnAla 1295 1300 1305 aac ggg ggc cct ccc gac ccg ggc ttc ctg cgt ccg cagcga gca gcc 4047 Asn Gly Gly Pro Pro Asp Pro Gly Phe Leu Arg Pro Gln ArgAla Ala 1310 1315 1320 1325 ctc tat atc ctt ggg gac aaa gcc cag ctc aagggt gtg cgg tca gac 4095 Leu Tyr Ile Leu Gly Asp Lys Ala Gln Leu Lys GlyVal Arg Ser Asp 1330 1335 1340 ccc ctg cag cag tgg gag ctg gtg ccc attgag gta ttc gag gca cgg 4143 Pro Leu Gln Gln Trp Glu Leu Val Pro Ile GluVal Phe Glu Ala Arg 1345 1350 1355 cag gtg aag gct agc ttc aag aag ctgctg aaa gca tgt gtc cca ggc 4191 Gln Val Lys Ala Ser Phe Lys Lys Leu LeuLys Ala Cys Val Pro Gly 1360 1365 1370 tgc ccc gct gct gag ccc agc ccagcc tcc ttc ctg cgc tca ctg gag 4239 Cys Pro Ala Ala Glu Pro Ser Pro AlaSer Phe Leu Arg Ser Leu Glu 1375 1380 1385 gac tca gag tgg ctg atc cagatc cac aag ctg ctg cag gtg tct gtg 4287 Asp Ser Glu Trp Leu Ile Gln IleHis Lys Leu Leu Gln Val Ser Val 1390 1395 1400 1405 ctg gtg gtg gag ctcctg gat tca ggc tcc tcc gtg ctg gtg ggc ctg 4335 Leu Val Val Glu Leu LeuAsp Ser Gly Ser Ser Val Leu Val Gly Leu 1410 1415 1420 gag gat ggc tgggac atc acc acc cag gtg gta tcc ttg gtg cag ctg 4383 Glu Asp Gly Trp AspIle Thr Thr Gln Val Val Ser Leu Val Gln Leu 1425 1430 1435 ctc tca gacccc ttc tac cgc acg ctg gag ggc ttt cgc ctg ctg gtg 4431 Leu Ser Asp ProPhe Tyr Arg Thr Leu Glu Gly Phe Arg Leu Leu Val 1440 1445 1450 gag aaggag tgg ctg tcc ttc ggc cat cgc ttc agc cac cgt gga gct 4479 Glu Lys GluTrp Leu Ser Phe Gly His Arg Phe Ser His Arg Gly Ala 1455 1460 1465 cacacc ctg gcc ggg cag agc agc ggc ttc aca ccc gtc ttc ctg cag 4527 His ThrLeu Ala Gly Gln Ser Ser Gly Phe Thr Pro Val Phe Leu Gln 1470 1475 14801485 ttc ctg gac tgc gta cac cag gtc cac ctg cag ttc ccc atg gag ttt4575 Phe Leu Asp Cys Val His Gln Val His Leu Gln Phe Pro Met Glu Phe1490 1495 1500 gag ttc agc cag ttc tac ctc aag ttc ctc ggc tac cac catgtg tcc 4623 Glu Phe Ser Gln Phe Tyr Leu Lys Phe Leu Gly Tyr His His ValSer 1505 1510 1515 cgc cgt ttc cgg acc ttc ctg ctc gac tct gac tat gagcgc att gag 4671 Arg Arg Phe Arg Thr Phe Leu Leu Asp Ser Asp Tyr Glu ArgIle Glu 1520 1525 1530 ctg ggg ctg ctg tat gag gag aag ggg gaa cgc aggggc cag gtg ccg 4719 Leu Gly Leu Leu Tyr Glu Glu Lys Gly Glu Arg Arg GlyGln Val Pro 1535 1540 1545 tgc agg tct gtg tgg gag tat gtg gac cgg ctgagc aag agg acg cct 4767 Cys Arg Ser Val Trp Glu Tyr Val Asp Arg Leu SerLys Arg Thr Pro 1550 1555 1560 1565 gtg ttc cac aat tac atg tat gcg cccgag gac gca gag gtc ctg cgg 4815 Val Phe His Asn Tyr Met Tyr Ala Pro GluAsp Ala Glu Val Leu Arg 1570 1575 1580 ccc tac agc aac gtg tcc aac ctgaag gtg tgg gac ttc tac act gag 4863 Pro Tyr Ser Asn Val Ser Asn Leu LysVal Trp Asp Phe Tyr Thr Glu 1585 1590 1595 gag acg ctg gcc gag gcc ctccct atg act ggg aac tgg ccc agg ggc 4911 Glu Thr Leu Ala Glu Ala Leu ProMet Thr Gly Asn Trp Pro Arg Gly 1600 1605 1610 ccc ctg aac ccc cag aggaag aac ggt ctg atg gag gcg tcc cca gag 4959 Pro Leu Asn Pro Gln Arg LysAsn Gly Leu Met Glu Ala Ser Pro Glu 1615 1620 1625 cag cgc cgc gtg gtgtgg ccc tgt tac gac agc tgc ccg cgg gcc cag 5007 Gln Arg Arg Val Val TrpPro Cys Tyr Asp Ser Cys Pro Arg Ala Gln 1630 1635 1640 1645 cct gac gccatc tca cgc ctg ctg gag gag ctg cag agg ctg gag aca 5055 Pro Asp Ala IleSer Arg Leu Leu Glu Glu Leu Gln Arg Leu Glu Thr 1650 1655 1660 gag ttgggc caa ccc gct gag cgc tgg aag gac acc tgg gac cgg gtg 5103 Glu Leu GlyGln Pro Ala Glu Arg Trp Lys Asp Thr Trp Asp Arg Val 1665 1670 1675 aaggct gca cag cgc ctc gag ggc cgg cca gac ggc cgt ggc acc cct 5151 Lys AlaAla Gln Arg Leu Glu Gly Arg Pro Asp Gly Arg Gly Thr Pro 1680 1685 1690agc tcc ctc ctt gtg tcc acc gca ccc cac cac cgt cgc tcg ctg ggt 5199 SerSer Leu Leu Val Ser Thr Ala Pro His His Arg Arg Ser Leu Gly 1695 17001705 gtg tac ctg cag gag ggg ccc gtg ggc tcc acc ctg agc ctc agc ctg5247 Val Tyr Leu Gln Glu Gly Pro Val Gly Ser Thr Leu Ser Leu Ser Leu1710 1715 1720 1725 gac agc gac cag agt agt ggc tca acc aca tcc ggc tcccgt cag gct 5295 Asp Ser Asp Gln Ser Ser Gly Ser Thr Thr Ser Gly Ser ArgGln Ala 1730 1735 1740 gcc cgc cgc agc acc agc acc ctg tac agc cag ttccag aca gca gag 5343 Ala Arg Arg Ser Thr Ser Thr Leu Tyr Ser Gln Phe GlnThr Ala Glu 1745 1750 1755 agt gag aac agg tcc tac gag ggc act ctg tacaag aag ggg gcc ttc 5391 Ser Glu Asn Arg Ser Tyr Glu Gly Thr Leu Tyr LysLys Gly Ala Phe 1760 1765 1770 atg aag cct tgg aag gcc cgc tgg ttc gtgctg gac aag acc aag cac 5439 Met Lys Pro Trp Lys Ala Arg Trp Phe Val LeuAsp Lys Thr Lys His 1775 1780 1785 cag ctg cgc tac tac gac cac cgt gtggac aca gag tgc aag ggt gtc 5487 Gln Leu Arg Tyr Tyr Asp His Arg Val AspThr Glu Cys Lys Gly Val 1790 1795 1800 1805 atc gac ttg gcg gag gtg gaggct gtg gca cct ggc acg ccc act atg 5535 Ile Asp Leu Ala Glu Val Glu AlaVal Ala Pro Gly Thr Pro Thr Met 1810 1815 1820 ggt gcc cct aag act gtggac gag aag gcc ttc ttt gac gtg aag aca 5583 Gly Ala Pro Lys Thr Val AspGlu Lys Ala Phe Phe Asp Val Lys Thr 1825 1830 1835 acg cgt cgc gtt tacaac ttc tgt gcc cag gac gtg ccc tcg gcc cag 5631 Thr Arg Arg Val Tyr AsnPhe Cys Ala Gln Asp Val Pro Ser Ala Gln 1840 1845 1850 cag tgg gtg gaccgg atc cag agc tgc tgt cgg acg cct gag cct ccc 5679 Gln Trp Val Asp ArgIle Gln Ser Cys Cys Arg Thr Pro Glu Pro Pro 1855 1860 1865 agc cct gcccgg ctg ctc tgc tct cgt tac cga cca cta ggg gtg gca 5727 Ser Pro Ala ArgLeu Leu Cys Ser Arg Tyr Arg Pro Leu Gly Val Ala 1870 1875 1880 1885 gggccg ccc cgg cca tgt tta cag ccc cgg ccc tcg aca gta ctg agc 5775 Gly ProPro Arg Pro Cys Leu Gln Pro Arg Pro Ser Thr Val Leu Ser 1890 1895 1900ccc gag ccc cca gca ctt gtg tgt aca gcc ccc gtc ccc gcc ccg ccc 5823 ProGlu Pro Pro Ala Leu Val Cys Thr Ala Pro Val Pro Ala Pro Pro 1905 19101915 cgc ccg gcc ggc cct aac tta ttt tgg cgt cac agc tgagcaccgt 5869 ArgPro Ala Gly Pro Asn Leu Phe Trp Arg His Ser 1920 1925 gccgggaggtggccaaggta cagcccgcaa tgggcctgta aatagtccgg ccccgtcagc 5929 gtgtgctggtccacgggctc aggcgagttt ctagaaagag tctatataaa gagagaacta 5989 acgc 5993 581929 PRT Homo sapiens 58 Met Ala Arg Leu Ala Asp Tyr Phe Val Leu Val AlaPhe Gly Pro His 1 5 10 15 Pro Arg Gly Ser Gly Glu Gly Gln Gly Gln IleLeu Gln Arg Phe Pro 20 25 30 Glu Lys Asp Trp Glu Asp Asn Pro Phe Pro GlnGly Ile Glu Leu Phe 35 40 45 Cys Gln Pro Ser Gly Trp Gln Leu Cys Pro GluArg Asn Pro Pro Thr 50 55 60 Phe Phe Val Ala Val Leu Thr Asp Ile Asn SerGlu Arg His Tyr Cys 65 70 75 80 Ala Cys Leu Thr Phe Trp Glu Pro Ala GluPro Ser Gln Glu Thr Thr 85 90 95 Arg Val Glu Asp Ala Thr Glu Arg Glu GluGlu Gly Asp Glu Gly Gly 100 105 110 Gln Thr His Leu Ser Pro Thr Ala ProAla Pro Ser Ala Gln Leu Phe 115 120 125 Ala Pro Lys Thr Leu Val Leu ValSer Arg Leu Asp His Thr Glu Val 130 135 140 Phe Arg Asn Ser Leu Gly LeuIle Tyr Ala Ile His Val Glu Gly Leu 145 150 155 160 Asn Val Cys Leu GluAsn Val Ile Gly Asn Leu Leu Thr Cys Thr Val 165 170 175 Pro Leu Ala GlyGly Ser Gln Arg Thr Ile Ser Leu Gly Ala Gly Asp 180 185 190 Arg Gln ValIle Gln Thr Pro Leu Ala Asp Ser Leu Pro Val Ser Arg 195 200 205 Cys SerVal Ala Leu Leu Phe Arg Gln Leu Gly Ile Thr Asn Val Leu 210 215 220 SerLeu Phe Cys Ala Ala Leu Thr Glu His Lys Val Leu Phe Leu Ser 225 230 235240 Arg Ser Tyr Gln Arg Leu Ala Asp Ala Cys Arg Gly Leu Leu Ala Leu 245250 255 Leu Phe Pro Leu Arg Tyr Ser Phe Thr Tyr Val Pro Ile Leu Pro Ala260 265 270 Gln Leu Leu Glu Val Leu Ser Thr Pro Thr Pro Phe Ile Ile GlyVal 275 280 285 Asn Ala Ala Phe Gln Ala Glu Thr Gln Glu Leu Leu Asp ValIle Val 290 295 300 Ala Asp Leu Asp Gly Gly Thr Val Thr Ile Pro Glu CysVal His Ile 305 310 315 320 Pro Pro Leu Pro Glu Pro Leu Gln Ser Gln ThrHis Ser Val Leu Ser 325 330 335 Met Val Leu Asp Pro Glu Leu Glu Leu AlaAsp Leu Ala Phe Pro Pro 340 345 350 Pro Thr Thr Ser Thr Ser Ser Leu LysMet Gln Asp Lys Glu Leu Arg 355 360 365 Ala Val Phe Leu Arg Leu Phe AlaGln Leu Leu Gln Gly Tyr Arg Trp 370 375 380 Cys Leu His Val Val Arg IleHis Pro Glu Pro Val Ile Arg Phe His 385 390 395 400 Lys Ala Ala Phe LeuGly Gln Arg Gly Leu Val Glu Asp Asp Phe Leu 405 410 415 Met Lys Val LeuGlu Gly Met Ala Phe Ala Gly Phe Val Ser Glu Arg 420 425 430 Gly Val ProTyr Arg Pro Thr Asp Leu Phe Asp Glu Leu Val Ala His 435 440 445 Glu ValAla Arg Met Arg Ala Asp Glu Asn His Pro Gln Arg Val Leu 450 455 460 ArgHis Val Gln Glu Leu Ala Glu Gln Leu Tyr Lys Asn Glu Asn Pro 465 470 475480 Tyr Pro Ala Val Ala Met His Lys Val Gln Arg Pro Gly Glu Ser Ser 485490 495 His Leu Arg Arg Val Pro Arg Pro Phe Pro Arg Leu Asp Glu Gly Thr500 505 510 Val Gln Trp Ile Val Asp Gln Ala Ala Ala Lys Met Gln Gly AlaPro 515 520 525 Pro Ala Val Lys Ala Glu Arg Arg Thr Thr Val Pro Ser GlyPro Pro 530 535 540 Met Thr Ala Ile Leu Glu Arg Cys Ser Gly Leu His ValAsn Ser Ala 545 550 555 560 Arg Arg Leu Glu Val Val Arg Asn Cys Ile SerTyr Val Phe Glu Gly 565 570 575 Lys Met Leu Glu Ala Lys Lys Leu Leu ProAla Val Leu Arg Ala Leu 580 585 590 Lys Gly Arg Val Ala Arg Arg Cys LeuAla Gln Glu Leu His Leu His 595 600 605 Val Gln Gln Asn Arg Ala Val LeuAsp His Gln Gln Phe Asp Phe Val 610 615 620 Val Arg Met Met Asn Cys CysLeu Gln Asp Cys Thr Ser Leu Asp Glu 625 630 635 640 His Gly Ile Ala AlaAla Leu Leu Pro Leu Val Thr Ala Phe Cys Arg 645 650 655 Lys Leu Ser ProGly Val Thr Gln Phe Ala Tyr Ser Cys Val Gln Glu 660 665 670 His Val ValTrp Ser Thr Pro Gln Phe Trp Glu Ala Met Phe Tyr Gly 675 680 685 Asp ValGln Thr His Ile Arg Ala Leu Tyr Leu Glu Pro Thr Glu Asp 690 695 700 LeuAla Pro Ala Gln Glu Val Gly Glu Ala Pro Ser Gln Glu Asp Glu 705 710 715720 Arg Ser Ala Leu Asp Val Ala Ser Glu Gln Arg Arg Leu Trp Pro Thr 725730 735 Leu Ser Arg Glu Lys Gln Gln Glu Leu Val Gln Lys Glu Glu Ser Thr740 745 750 Val Phe Ser Gln Ala Ile His Tyr Ala Asn Arg Met Ser Tyr LeuLeu 755 760 765 Leu Pro Leu Asp Ser Ser Lys Ser Arg Leu Leu Arg Glu ArgAla Gly 770 775 780 Leu Gly Asp Leu Glu Ser Ala Ser Asn Ser Leu Val ThrAsn Ser Met 785 790 795 800 Ala Gly Ser Val Ala Glu Ser Tyr Asp Thr GluSer Gly Phe Glu Asp 805 810 815 Ala Glu Thr Cys Asp Val Ala Gly Ala ValVal Arg Phe Ile Asn Arg 820 825 830 Phe Val Asp Lys Val Cys Thr Glu SerGly Val Thr Ser Asp His Leu 835 840 845 Lys Gly Leu His Val Met Val ProAsp Ile Val Gln Met His Ile Glu 850 855 860 Thr Leu Glu Ala Val Gln ArgGlu Ser Arg Arg Leu Pro Pro Ile Gln 865 870 875 880 Lys Pro Lys Leu LeuArg Pro Arg Leu Leu Pro Gly Glu Glu Cys Val 885 890 895 Leu Asp Gly LeuArg Val Tyr Leu Leu Pro Asp Gly Arg Glu Glu Gly 900 905 910 Ala Gly GlySer Ala Gly Gly Pro Ala Leu Leu Pro Ala Glu Gly Ala 915 920 925 Val PheLeu Thr Thr Tyr Arg Val Ile Phe Thr Gly Met Pro Thr Asp 930 935 940 ProLeu Val Gly Glu Gln Val Val Val Arg Ser Phe Pro Val Ala Ala 945 950 955960 Leu Thr Lys Glu Lys Arg Ile Ser Val Gln Thr Pro Val Asp Gln Leu 965970 975 Leu Gln Asp Gly Leu Gln Leu Arg Ser Cys Thr Phe Gln Leu Leu Lys980 985 990 Met Ala Phe Asp Glu Glu Val Gly Ser Asp Ser Ala Glu Leu PheArg 995 1000 1005 Lys Gln Leu His Lys Leu Arg Tyr Pro Pro Asp Ile ArgAla Thr Phe 1010 1015 1020 Ala Phe Thr Leu Gly Ser Ala His Thr Pro GlyArg Pro Pro Arg Val 1025 1030 1035 1040 Thr Lys Asp Lys Gly Pro Ser LeuArg Thr Leu Ser Arg Asn Leu Val 1045 1050 1055 Lys Asn Ala Lys Lys ThrIle Gly Arg Gln His Val Thr Arg Lys Lys 1060 1065 1070 Tyr Asn Pro ProSer Trp Glu His Arg Gly Gln Pro Pro Pro Glu Asp 1075 1080 1085 Gln GluAsp Glu Ile Ser Val Ser Glu Glu Leu Glu Pro Ser Thr Leu 1090 1095 1100Thr Pro Ser Ser Ala Leu Lys Pro Ser Asp Arg Met Thr Met Ser Ser 11051110 1115 1120 Leu Val Glu Arg Ala Cys Cys Arg Asp Tyr Gln Arg Leu GlyLeu Gly 1125 1130 1135 Thr Leu Ser Ser Ser Leu Ser Arg Ala Lys Ser GluPro Phe Arg Ile 1140 1145 1150 Ser Pro Val Asn Arg Met Tyr Ala Ile CysArg Ser Tyr Pro Gly Leu 1155 1160 1165 Leu Ile Val Arg Gln Ser Val GlnAsp Asn Ala Leu Gln Arg Val Ser 1170 1175 1180 Arg Cys Tyr Arg Gln AsnArg Phe Pro Val Val Cys Trp Arg Ser Gly 1185 1190 1195 1200 Arg Ser LysAla Val Leu Leu Arg Ser Gly Gly Leu His Gly Lys Gly 1205 1210 1215 ValVal Gly Leu Phe Lys Ala Gln Asn Ala Pro Ser Pro Gly Gln Ser 1220 12251230 Gln Ala Asp Ser Ser Ser Leu Glu Gln Glu Lys Tyr Leu Gln Ala Val1235 1240 1245 Val Ser Ser Met Pro Arg Tyr Ala Asp Ala Ser Gly Arg AsnThr Leu 1250 1255 1260 Ser Gly Phe Ser Ser Ala His Met Gly Ser His GlyLys Trp Gly Ser 1265 1270 1275 1280 Val Arg Thr Ser Gly Arg Ser Ser GlyLeu Gly Thr Asp Val Gly Ser 1285 1290 1295 Arg Leu Ala Gly Arg Asp AlaLeu Ala Pro Pro Gln Ala Asn Gly Gly 1300 1305 1310 Pro Pro Asp Pro GlyPhe Leu Arg Pro Gln Arg Ala Ala Leu Tyr Ile 1315 1320 1325 Leu Gly AspLys Ala Gln Leu Lys Gly Val Arg Ser Asp Pro Leu Gln 1330 1335 1340 GlnTrp Glu Leu Val Pro Ile Glu Val Phe Glu Ala Arg Gln Val Lys 1345 13501355 1360 Ala Ser Phe Lys Lys Leu Leu Lys Ala Cys Val Pro Gly Cys ProAla 1365 1370 1375 Ala Glu Pro Ser Pro Ala Ser Phe Leu Arg Ser Leu GluAsp Ser Glu 1380 1385 1390 Trp Leu Ile Gln Ile His Lys Leu Leu Gln ValSer Val Leu Val Val 1395 1400 1405 Glu Leu Leu Asp Ser Gly Ser Ser ValLeu Val Gly Leu Glu Asp Gly 1410 1415 1420 Trp Asp Ile Thr Thr Gln ValVal Ser Leu Val Gln Leu Leu Ser Asp 1425 1430 1435 1440 Pro Phe Tyr ArgThr Leu Glu Gly Phe Arg Leu Leu Val Glu Lys Glu 1445 1450 1455 Trp LeuSer Phe Gly His Arg Phe Ser His Arg Gly Ala His Thr Leu 1460 1465 1470Ala Gly Gln Ser Ser Gly Phe Thr Pro Val Phe Leu Gln Phe Leu Asp 14751480 1485 Cys Val His Gln Val His Leu Gln Phe Pro Met Glu Phe Glu PheSer 1490 1495 1500 Gln Phe Tyr Leu Lys Phe Leu Gly Tyr His His Val SerArg Arg Phe 1505 1510 1515 1520 Arg Thr Phe Leu Leu Asp Ser Asp Tyr GluArg Ile Glu Leu Gly Leu 1525 1530 1535 Leu Tyr Glu Glu Lys Gly Glu ArgArg Gly Gln Val Pro Cys Arg Ser 1540 1545 1550 Val Trp Glu Tyr Val AspArg Leu Ser Lys Arg Thr Pro Val Phe His 1555 1560 1565 Asn Tyr Met TyrAla Pro Glu Asp Ala Glu Val Leu Arg Pro Tyr Ser 1570 1575 1580 Asn ValSer Asn Leu Lys Val Trp Asp Phe Tyr Thr Glu Glu Thr Leu 1585 1590 15951600 Ala Glu Ala Leu Pro Met Thr Gly Asn Trp Pro Arg Gly Pro Leu Asn1605 1610 1615 Pro Gln Arg Lys Asn Gly Leu Met Glu Ala Ser Pro Glu GlnArg Arg 1620 1625 1630 Val Val Trp Pro Cys Tyr Asp Ser Cys Pro Arg AlaGln Pro Asp Ala 1635 1640 1645 Ile Ser Arg Leu Leu Glu Glu Leu Gln ArgLeu Glu Thr Glu Leu Gly 1650 1655 1660 Gln Pro Ala Glu Arg Trp Lys AspThr Trp Asp Arg Val Lys Ala Ala 1665 1670 1675 1680 Gln Arg Leu Glu GlyArg Pro Asp Gly Arg Gly Thr Pro Ser Ser Leu 1685 1690 1695 Leu Val SerThr Ala Pro His His Arg Arg Ser Leu Gly Val Tyr Leu 1700 1705 1710 GlnGlu Gly Pro Val Gly Ser Thr Leu Ser Leu Ser Leu Asp Ser Asp 1715 17201725 Gln Ser Ser Gly Ser Thr Thr Ser Gly Ser Arg Gln Ala Ala Arg Arg1730 1735 1740 Ser Thr Ser Thr Leu Tyr Ser Gln Phe Gln Thr Ala Glu SerGlu Asn 1745 1750 1755 1760 Arg Ser Tyr Glu Gly Thr Leu Tyr Lys Lys GlyAla Phe Met Lys Pro 1765 1770 1775 Trp Lys Ala Arg Trp Phe Val Leu AspLys Thr Lys His Gln Leu Arg 1780 1785 1790 Tyr Tyr Asp His Arg Val AspThr Glu Cys Lys Gly Val Ile Asp Leu 1795 1800 1805 Ala Glu Val Glu AlaVal Ala Pro Gly Thr Pro Thr Met Gly Ala Pro 1810 1815 1820 Lys Thr ValAsp Glu Lys Ala Phe Phe Asp Val Lys Thr Thr Arg Arg 1825 1830 1835 1840Val Tyr Asn Phe Cys Ala Gln Asp Val Pro Ser Ala Gln Gln Trp Val 18451850 1855 Asp Arg Ile Gln Ser Cys Cys Arg Thr Pro Glu Pro Pro Ser ProAla 1860 1865 1870 Arg Leu Leu Cys Ser Arg Tyr Arg Pro Leu Gly Val AlaGly Pro Pro 1875 1880 1885 Arg Pro Cys Leu Gln Pro Arg Pro Ser Thr ValLeu Ser Pro Glu Pro 1890 1895 1900 Pro Ala Leu Val Cys Thr Ala Pro ValPro Ala Pro Pro Arg Pro Ala 1905 1910 1915 1920 Gly Pro Asn Leu Phe TrpArg His Ser 1925 59 2680 DNA Homo sapiens CDS (25)..(2601) 59 tccgacgccgtcgctgggac caag atg gac ctc ccg gcg ctg ctc ccc gcc 51 Met Asp Leu ProAla Leu Leu Pro Ala 1 5 ccg act gcg cgc gga ggg caa cat ggc ggc ggc cccggc ccg ctc cgc 99 Pro Thr Ala Arg Gly Gly Gln His Gly Gly Gly Pro GlyPro Leu Arg 10 15 20 25 cga gcc cca gcg ccg ctc ggc gcg agc ccc gcg cgccgc cgc ctg cta 147 Arg Ala Pro Ala Pro Leu Gly Ala Ser Pro Ala Arg ArgArg Leu Leu 30 35 40 ctg gtg cgg ggc cct gaa gat ggc ggg ccc ggg gcg cggccc ggg gag 195 Leu Val Arg Gly Pro Glu Asp Gly Gly Pro Gly Ala Arg ProGly Glu 45 50 55 gcc tcc ggg cca agc ccg ccg ccc gcc gag gac gac agc gacggc gac 243 Ala Ser Gly Pro Ser Pro Pro Pro Ala Glu Asp Asp Ser Asp GlyAsp 60 65 70 tct ttc ttg gtg ctg ctg gaa gtg ccg cac ggc ggc gct gcc gccgag 291 Ser Phe Leu Val Leu Leu Glu Val Pro His Gly Gly Ala Ala Ala Glu75 80 85 gct gcc gga tca cag gag gcc gag cct ggc tcc cgt gtc aac ctg gcg339 Ala Ala Gly Ser Gln Glu Ala Glu Pro Gly Ser Arg Val Asn Leu Ala 9095 100 105 agc cgc ccc gag cag ggc ccc agc ggc ccg gcc gcc ccc ccc ggccct 387 Ser Arg Pro Glu Gln Gly Pro Ser Gly Pro Ala Ala Pro Pro Gly Pro110 115 120 ggc gta gcc ccg gcg ggc gcc gtc acc atc agc agc cag gac ctgctg 435 Gly Val Ala Pro Ala Gly Ala Val Thr Ile Ser Ser Gln Asp Leu Leu125 130 135 gtg cgt ctc gac cgc ggc gtc ctc gcg ctg tct gcg ccg ccc ggcccc 483 Val Arg Leu Asp Arg Gly Val Leu Ala Leu Ser Ala Pro Pro Gly Pro140 145 150 gca acc gcg ggc gcc gcc gct ccc cgc cgc gcg ccc cag ggc ctcggc 531 Ala Thr Ala Gly Ala Ala Ala Pro Arg Arg Ala Pro Gln Gly Leu Gly155 160 165 ccc agc acg ccc ggc tac cgc tgc ccc gag ccg cag tgc gcg ctggcc 579 Pro Ser Thr Pro Gly Tyr Arg Cys Pro Glu Pro Gln Cys Ala Leu Ala170 175 180 185 ttc gcc aag aag cac cag ctc aag gtg cac ctg ctc acg cacggc ggc 627 Phe Ala Lys Lys His Gln Leu Lys Val His Leu Leu Thr His GlyGly 190 195 200 ggt cag ggc cgg cgg ccc ttc aag tgc cca ctg gag ggc tgtggt tgg 675 Gly Gln Gly Arg Arg Pro Phe Lys Cys Pro Leu Glu Gly Cys GlyTrp 205 210 215 gcc ttc aca acg tcc tac aag ctc aag cgg cac ctg cag tcgcac gac 723 Ala Phe Thr Thr Ser Tyr Lys Leu Lys Arg His Leu Gln Ser HisAsp 220 225 230 aag ctg cgg ccc ttc ggc tgt cca gtg ggc ggc tgt ggc aagaag ttc 771 Lys Leu Arg Pro Phe Gly Cys Pro Val Gly Gly Cys Gly Lys LysPhe 235 240 245 act acg gtc tat aac ctc aag gcg cac atg aag ggc cac gagcag gag 819 Thr Thr Val Tyr Asn Leu Lys Ala His Met Lys Gly His Glu GlnGlu 250 255 260 265 agc ctg ttc aag tgc gag gtg tgc gcc gag cgc ttc cccacg cac gcc 867 Ser Leu Phe Lys Cys Glu Val Cys Ala Glu Arg Phe Pro ThrHis Ala 270 275 280 aag ctc agc tcc cac cag cgc agc cac ttc gag ccc gagcgc cct tac 915 Lys Leu Ser Ser His Gln Arg Ser His Phe Glu Pro Glu ArgPro Tyr 285 290 295 aag tgt gac ttt ccc ggt tgt gag aag aca ttt atc acagtg agt gcc 963 Lys Cys Asp Phe Pro Gly Cys Glu Lys Thr Phe Ile Thr ValSer Ala 300 305 310 ctg ttt tcc cat aac cga gcc cac ttc agg gaa caa gagctc ttt tcc 1011 Leu Phe Ser His Asn Arg Ala His Phe Arg Glu Gln Glu LeuPhe Ser 315 320 325 tgc tcc ttt cct ggg tgc acg agg aag cag tat gat aaagcc tgt cgg 1059 Cys Ser Phe Pro Gly Cys Thr Arg Lys Gln Tyr Asp Lys AlaCys Arg 330 335 340 345 ctg aaa att cac ctg cgg agc cat aca ggt gaa agacca ttt att tgt 1107 Leu Lys Ile His Leu Arg Ser His Thr Gly Glu Arg ProPhe Ile Cys 350 355 360 gac tct gac agc tgt ggc tgg acc ttc acc agc atgtcc aaa ctt cta 1155 Asp Ser Asp Ser Cys Gly Trp Thr Phe Thr Ser Met SerLys Leu Leu 365 370 375 agg cac aga agg aaa cat gac gat gac cgg agg tttacc tgc cct gtc 1203 Arg His Arg Arg Lys His Asp Asp Asp Arg Arg Phe ThrCys Pro Val 380 385 390 gag ggc tgt ggg aaa tca ttc acc aga gca gag catctg aaa ggc cac 1251 Glu Gly Cys Gly Lys Ser Phe Thr Arg Ala Glu His LeuLys Gly His 395 400 405 agc ata acc cac cta ggc aca aag ccg ttc gag tgtcct gtg gaa gga 1299 Ser Ile Thr His Leu Gly Thr Lys Pro Phe Glu Cys ProVal Glu Gly 410 415 420 425 tgt tgc gcg agg ttc tcc gct cgt agc agt ctgtac att cac tct aag 1347 Cys Cys Ala Arg Phe Ser Ala Arg Ser Ser Leu TyrIle His Ser Lys 430 435 440 aaa cac gtg cag gat gtg ggt gct ccg aaa agccgt tgc cca gtt tct 1395 Lys His Val Gln Asp Val Gly Ala Pro Lys Ser ArgCys Pro Val Ser 445 450 455 acc tgc aac aga ctc ttc acc tcc aag cac agcatg aag gcg cac atg 1443 Thr Cys Asn Arg Leu Phe Thr Ser Lys His Ser MetLys Ala His Met 460 465 470 gtc aga cag cac agc cgg cgc caa gat ctc ttacct cag cta gaa gct 1491 Val Arg Gln His Ser Arg Arg Gln Asp Leu Leu ProGln Leu Glu Ala 475 480 485 ccg agt tct ctt act ccc agc agt gaa ctc agcagc cca ggc caa agt 1539 Pro Ser Ser Leu Thr Pro Ser Ser Glu Leu Ser SerPro Gly Gln Ser 490 495 500 505 gag ctc act aac atg gat ctt gct gca ctcttc tct gac aca cct gcc 1587 Glu Leu Thr Asn Met Asp Leu Ala Ala Leu PheSer Asp Thr Pro Ala 510 515 520 aat gct agt ggt tct gca ggt ggg tcg gatgag gct ctg aac tcc gga 1635 Asn Ala Ser Gly Ser Ala Gly Gly Ser Asp GluAla Leu Asn Ser Gly 525 530 535 atc ctg act att gac gtc act tct gtg agctcc tct ctg gga ggg aac 1683 Ile Leu Thr Ile Asp Val Thr Ser Val Ser SerSer Leu Gly Gly Asn 540 545 550 ctc cct gct aat aat agc tcc cta ggg ccgatg gaa ccc ctg gtc ctg 1731 Leu Pro Ala Asn Asn Ser Ser Leu Gly Pro MetGlu Pro Leu Val Leu 555 560 565 gtg gcc cac agt gat att ccc cca agc ctggac agc cct ctg gtt ctc 1779 Val Ala His Ser Asp Ile Pro Pro Ser Leu AspSer Pro Leu Val Leu 570 575 580 585 ggg aca gca gcc acg gtt ctg cag cagggc agc ttc agt gtg gat gac 1827 Gly Thr Ala Ala Thr Val Leu Gln Gln GlySer Phe Ser Val Asp Asp 590 595 600 gtg cag act gtg agt gca gga gca ttaggc tgt ctg gtg gct ctg ccc 1875 Val Gln Thr Val Ser Ala Gly Ala Leu GlyCys Leu Val Ala Leu Pro 605 610 615 atg aag aac ttg agt gac gac cca ctggct ttg acc tcc aat agt aac 1923 Met Lys Asn Leu Ser Asp Asp Pro Leu AlaLeu Thr Ser Asn Ser Asn 620 625 630 tta gca gca cat atc acc aca ccg acctct tcg agc acc ccc cga gaa 1971 Leu Ala Ala His Ile Thr Thr Pro Thr SerSer Ser Thr Pro Arg Glu 635 640 645 aat gcc agt gtc ccg gaa ctg ctg gctcca atc aag gtg gag ccg gac 2019 Asn Ala Ser Val Pro Glu Leu Leu Ala ProIle Lys Val Glu Pro Asp 650 655 660 665 tcg cct tct cgc cca gga gca gttggg cag cag gaa gga agc cat ggg 2067 Ser Pro Ser Arg Pro Gly Ala Val GlyGln Gln Glu Gly Ser His Gly 670 675 680 ctg ccc cag tcc acg ttg ccc agtcca gca gag cag cac ggt gcc cag 2115 Leu Pro Gln Ser Thr Leu Pro Ser ProAla Glu Gln His Gly Ala Gln 685 690 695 gac aca gag ctc agt gca ggc actggc aac ttc tat ttg gaa agt ggg 2163 Asp Thr Glu Leu Ser Ala Gly Thr GlyAsn Phe Tyr Leu Glu Ser Gly 700 705 710 ggc tca gca aga act gat tac cgagcc att caa cta gcc aag gaa aaa 2211 Gly Ser Ala Arg Thr Asp Tyr Arg AlaIle Gln Leu Ala Lys Glu Lys 715 720 725 aag cag aga gga gcg ggg agc aatgca gga gcc tca cag tct act cag 2259 Lys Gln Arg Gly Ala Gly Ser Asn AlaGly Ala Ser Gln Ser Thr Gln 730 735 740 745 aga aaa ata aaa gaa ggc aaaatg agt cct ccc cat ttc cat gca agc 2307 Arg Lys Ile Lys Glu Gly Lys MetSer Pro Pro His Phe His Ala Ser 750 755 760 cag aac agt tgg ttg tgt gggagc ctc gtg gtg ccc agc gga gga cgg 2355 Gln Asn Ser Trp Leu Cys Gly SerLeu Val Val Pro Ser Gly Gly Arg 765 770 775 cca gga cca gct cca gca gctggg gtg cag tgc ggg gcg cag ggc gtc 2403 Pro Gly Pro Ala Pro Ala Ala GlyVal Gln Cys Gly Ala Gln Gly Val 780 785 790 cag gtc cag ctg gtg cag gatgac ccc tcc ggc gaa ggt gtc ctg ccc 2451 Gln Val Gln Leu Val Gln Asp AspPro Ser Gly Glu Gly Val Leu Pro 795 800 805 tcg gcc cgc ggc cca gcc accttc ctc ccc ttc ctc act gtg gac ctg 2499 Ser Ala Arg Gly Pro Ala Thr PheLeu Pro Phe Leu Thr Val Asp Leu 810 815 820 825 ccc gtc tac gtc ctc caggag gtg ctc ccc tca tct gga ggc cct gct 2547 Pro Val Tyr Val Leu Gln GluVal Leu Pro Ser Ser Gly Gly Pro Ala 830 835 840 gga ccg gag gcc acc cagttc cca gga agc act atc aac ctg cag gat 2595 Gly Pro Glu Ala Thr Gln PhePro Gly Ser Thr Ile Asn Leu Gln Asp 845 850 855 ctg cag tgacggcagcctcggcctgg gcaggcccaa ggccacggtc taggacacac 2651 Leu Gln cttccctgagactcatgaca tgagcctgg 2680 60 859 PRT Homo sapiens 60 Met Asp Leu Pro AlaLeu Leu Pro Ala Pro Thr Ala Arg Gly Gly Gln 1 5 10 15 His Gly Gly GlyPro Gly Pro Leu Arg Arg Ala Pro Ala Pro Leu Gly 20 25 30 Ala Ser Pro AlaArg Arg Arg Leu Leu Leu Val Arg Gly Pro Glu Asp 35 40 45 Gly Gly Pro GlyAla Arg Pro Gly Glu Ala Ser Gly Pro Ser Pro Pro 50 55 60 Pro Ala Glu AspAsp Ser Asp Gly Asp Ser Phe Leu Val Leu Leu Glu 65 70 75 80 Val Pro HisGly Gly Ala Ala Ala Glu Ala Ala Gly Ser Gln Glu Ala 85 90 95 Glu Pro GlySer Arg Val Asn Leu Ala Ser Arg Pro Glu Gln Gly Pro 100 105 110 Ser GlyPro Ala Ala Pro Pro Gly Pro Gly Val Ala Pro Ala Gly Ala 115 120 125 ValThr Ile Ser Ser Gln Asp Leu Leu Val Arg Leu Asp Arg Gly Val 130 135 140Leu Ala Leu Ser Ala Pro Pro Gly Pro Ala Thr Ala Gly Ala Ala Ala 145 150155 160 Pro Arg Arg Ala Pro Gln Gly Leu Gly Pro Ser Thr Pro Gly Tyr Arg165 170 175 Cys Pro Glu Pro Gln Cys Ala Leu Ala Phe Ala Lys Lys His GlnLeu 180 185 190 Lys Val His Leu Leu Thr His Gly Gly Gly Gln Gly Arg ArgPro Phe 195 200 205 Lys Cys Pro Leu Glu Gly Cys Gly Trp Ala Phe Thr ThrSer Tyr Lys 210 215 220 Leu Lys Arg His Leu Gln Ser His Asp Lys Leu ArgPro Phe Gly Cys 225 230 235 240 Pro Val Gly Gly Cys Gly Lys Lys Phe ThrThr Val Tyr Asn Leu Lys 245 250 255 Ala His Met Lys Gly His Glu Gln GluSer Leu Phe Lys Cys Glu Val 260 265 270 Cys Ala Glu Arg Phe Pro Thr HisAla Lys Leu Ser Ser His Gln Arg 275 280 285 Ser His Phe Glu Pro Glu ArgPro Tyr Lys Cys Asp Phe Pro Gly Cys 290 295 300 Glu Lys Thr Phe Ile ThrVal Ser Ala Leu Phe Ser His Asn Arg Ala 305 310 315 320 His Phe Arg GluGln Glu Leu Phe Ser Cys Ser Phe Pro Gly Cys Thr 325 330 335 Arg Lys GlnTyr Asp Lys Ala Cys Arg Leu Lys Ile His Leu Arg Ser 340 345 350 His ThrGly Glu Arg Pro Phe Ile Cys Asp Ser Asp Ser Cys Gly Trp 355 360 365 ThrPhe Thr Ser Met Ser Lys Leu Leu Arg His Arg Arg Lys His Asp 370 375 380Asp Asp Arg Arg Phe Thr Cys Pro Val Glu Gly Cys Gly Lys Ser Phe 385 390395 400 Thr Arg Ala Glu His Leu Lys Gly His Ser Ile Thr His Leu Gly Thr405 410 415 Lys Pro Phe Glu Cys Pro Val Glu Gly Cys Cys Ala Arg Phe SerAla 420 425 430 Arg Ser Ser Leu Tyr Ile His Ser Lys Lys His Val Gln AspVal Gly 435 440 445 Ala Pro Lys Ser Arg Cys Pro Val Ser Thr Cys Asn ArgLeu Phe Thr 450 455 460 Ser Lys His Ser Met Lys Ala His Met Val Arg GlnHis Ser Arg Arg 465 470 475 480 Gln Asp Leu Leu Pro Gln Leu Glu Ala ProSer Ser Leu Thr Pro Ser 485 490 495 Ser Glu Leu Ser Ser Pro Gly Gln SerGlu Leu Thr Asn Met Asp Leu 500 505 510 Ala Ala Leu Phe Ser Asp Thr ProAla Asn Ala Ser Gly Ser Ala Gly 515 520 525 Gly Ser Asp Glu Ala Leu AsnSer Gly Ile Leu Thr Ile Asp Val Thr 530 535 540 Ser Val Ser Ser Ser LeuGly Gly Asn Leu Pro Ala Asn Asn Ser Ser 545 550 555 560 Leu Gly Pro MetGlu Pro Leu Val Leu Val Ala His Ser Asp Ile Pro 565 570 575 Pro Ser LeuAsp Ser Pro Leu Val Leu Gly Thr Ala Ala Thr Val Leu 580 585 590 Gln GlnGly Ser Phe Ser Val Asp Asp Val Gln Thr Val Ser Ala Gly 595 600 605 AlaLeu Gly Cys Leu Val Ala Leu Pro Met Lys Asn Leu Ser Asp Asp 610 615 620Pro Leu Ala Leu Thr Ser Asn Ser Asn Leu Ala Ala His Ile Thr Thr 625 630635 640 Pro Thr Ser Ser Ser Thr Pro Arg Glu Asn Ala Ser Val Pro Glu Leu645 650 655 Leu Ala Pro Ile Lys Val Glu Pro Asp Ser Pro Ser Arg Pro GlyAla 660 665 670 Val Gly Gln Gln Glu Gly Ser His Gly Leu Pro Gln Ser ThrLeu Pro 675 680 685 Ser Pro Ala Glu Gln His Gly Ala Gln Asp Thr Glu LeuSer Ala Gly 690 695 700 Thr Gly Asn Phe Tyr Leu Glu Ser Gly Gly Ser AlaArg Thr Asp Tyr 705 710 715 720 Arg Ala Ile Gln Leu Ala Lys Glu Lys LysGln Arg Gly Ala Gly Ser 725 730 735 Asn Ala Gly Ala Ser Gln Ser Thr GlnArg Lys Ile Lys Glu Gly Lys 740 745 750 Met Ser Pro Pro His Phe His AlaSer Gln Asn Ser Trp Leu Cys Gly 755 760 765 Ser Leu Val Val Pro Ser GlyGly Arg Pro Gly Pro Ala Pro Ala Ala 770 775 780 Gly Val Gln Cys Gly AlaGln Gly Val Gln Val Gln Leu Val Gln Asp 785 790 795 800 Asp Pro Ser GlyGlu Gly Val Leu Pro Ser Ala Arg Gly Pro Ala Thr 805 810 815 Phe Leu ProPhe Leu Thr Val Asp Leu Pro Val Tyr Val Leu Gln Glu 820 825 830 Val LeuPro Ser Ser Gly Gly Pro Ala Gly Pro Glu Ala Thr Gln Phe 835 840 845 ProGly Ser Thr Ile Asn Leu Gln Asp Leu Gln 850 855 61 379 DNA Homo sapiensCDS (10)..(345) 61 taattaaat atg gga caa ggt gtg ctg aag aag act act ggtcct gtg aga 51 Met Gly Gln Gly Val Leu Lys Lys Thr Thr Gly Pro Val Arg 15 10 ttg gct gta tgt gag aat cca cat gag agg cta aga ata ttg tac aca 99Leu Ala Val Cys Glu Asn Pro His Glu Arg Leu Arg Ile Leu Tyr Thr 15 20 2530 aag atc ctt gat gtt ctt gag caa atc cct aaa aat gca gca tat aaa 147Lys Ile Leu Asp Val Leu Glu Gln Ile Pro Lys Asn Ala Ala Tyr Lys 35 40 45aag tgt aca gaa cag att aca aat gag aag cta gct atg ctt aaa gta 195 LysCys Thr Glu Gln Ile Thr Asn Glu Lys Leu Ala Met Leu Lys Val 50 55 60 gaacca gat gtt aaa aaa tta gaa gac caa ctt caa gat ggc caa ata 243 Glu ProAsp Val Lys Lys Leu Glu Asp Gln Leu Gln Asp Gly Gln Ile 65 70 75 gaa gaggtg att cat cag gct gaa aat gaa cta aat gtg gtg aga aaa 291 Glu Glu ValIle His Gln Ala Glu Asn Glu Leu Asn Val Val Arg Lys 80 85 90 acg atg cagtgg aaa cca tgg ggg gca ata gtg gaa gag cct cct gcc 339 Thr Met Gln TrpLys Pro Trp Gly Ala Ile Val Glu Glu Pro Pro Ala 95 100 105 110 aat cagtgaaaacagc caatataatt attaaatgac tttg 379 Asn Gln 62 112 PRT Homosapiens 62 Met Gly Gln Gly Val Leu Lys Lys Thr Thr Gly Pro Val Arg LeuAla 1 5 10 15 Val Cys Glu Asn Pro His Glu Arg Leu Arg Ile Leu Tyr ThrLys Ile 20 25 30 Leu Asp Val Leu Glu Gln Ile Pro Lys Asn Ala Ala Tyr LysLys Cys 35 40 45 Thr Glu Gln Ile Thr Asn Glu Lys Leu Ala Met Leu Lys ValGlu Pro 50 55 60 Asp Val Lys Lys Leu Glu Asp Gln Leu Gln Asp Gly Gln IleGlu Glu 65 70 75 80 Val Ile His Gln Ala Glu Asn Glu Leu Asn Val Val ArgLys Thr Met 85 90 95 Gln Trp Lys Pro Trp Gly Ala Ile Val Glu Glu Pro ProAla Asn Gln 100 105 110 63 789 DNA Homo sapiens CDS (5)..(775) 63 agtgatg caa tgt cat ctt aat gga gcg act gtg aaa act gat gtg tgt 49 Met GlnCys His Leu Asn Gly Ala Thr Val Lys Thr Asp Val Cys 1 5 10 15 aga atgaaa gaa cac atg gaa gat aga gta aat gtg gca gat ttc aga 97 Arg Met LysGlu His Met Glu Asp Arg Val Asn Val Ala Asp Phe Arg 20 25 30 aaa cta gaatgg ctt ttc cca gaa aca aca gca aat ttt gat aaa ctg 145 Lys Leu Glu TrpLeu Phe Pro Glu Thr Thr Ala Asn Phe Asp Lys Leu 35 40 45 tta att caa tatcgg gga ttt tgt gct tac acg ttt gct gca aca gat 193 Leu Ile Gln Tyr ArgGly Phe Cys Ala Tyr Thr Phe Ala Ala Thr Asp 50 55 60 ggt ctt ctc ctt ccaggt aat cca gca att gga att tta aaa tat aaa 241 Gly Leu Leu Leu Pro GlyAsn Pro Ala Ile Gly Ile Leu Lys Tyr Lys 65 70 75 gaa aaa tat tac aca ttcaat agt aaa gat gct gca tat tca ttt gca 289 Glu Lys Tyr Tyr Thr Phe AsnSer Lys Asp Ala Ala Tyr Ser Phe Ala 80 85 90 95 gaa aat cct gaa cat tatatt gac ata gtt aga gaa aag gcc aaa aaa 337 Glu Asn Pro Glu His Tyr IleAsp Ile Val Arg Glu Lys Ala Lys Lys 100 105 110 aat aca gag tta att caacta ttg gaa ctt cat caa cag ttt gaa aca 385 Asn Thr Glu Leu Ile Gln LeuLeu Glu Leu His Gln Gln Phe Glu Thr 115 120 125 ttt att cca tat tct cagatg aga gat gct gac aaa cat tat ata aaa 433 Phe Ile Pro Tyr Ser Gln MetArg Asp Ala Asp Lys His Tyr Ile Lys 130 135 140 cca att aca aaa tgt gaaagt agc aca cag acg aat aca cac ata ctg 481 Pro Ile Thr Lys Cys Glu SerSer Thr Gln Thr Asn Thr His Ile Leu 145 150 155 cca cca acg att gtg agatca tat gag tgg aat gaa tgg gaa tta aga 529 Pro Pro Thr Ile Val Arg SerTyr Glu Trp Asn Glu Trp Glu Leu Arg 160 165 170 175 aga aaa gct ata aaattg gct aat ttg cgc cag aaa gtt act cac tca 577 Arg Lys Ala Ile Lys LeuAla Asn Leu Arg Gln Lys Val Thr His Ser 180 185 190 gta caa act gat cttagt cac ttg aga aga gaa aat tgt tcc caa gtg 625 Val Gln Thr Asp Leu SerHis Leu Arg Arg Glu Asn Cys Ser Gln Val 195 200 205 tac cct cca aag gacact agc acc cag tcc atg agg gaa gac agc act 673 Tyr Pro Pro Lys Asp ThrSer Thr Gln Ser Met Arg Glu Asp Ser Thr 210 215 220 ggg gtg ccc agg cctcag att tac ttg gct ggt ctt cgt gga gga aag 721 Gly Val Pro Arg Pro GlnIle Tyr Leu Ala Gly Leu Arg Gly Gly Lys 225 230 235 agc gaa atc acc gatgag gtc aag gtg aac tta act aga gat gtg gat 769 Ser Glu Ile Thr Asp GluVal Lys Val Asn Leu Thr Arg Asp Val Asp 240 245 250 255 gaa acctaattacaga caac 789 Glu Thr 64 257 PRT Homo sapiens 64 Met Gln Cys HisLeu Asn Gly Ala Thr Val Lys Thr Asp Val Cys Arg 1 5 10 15 Met Lys GluHis Met Glu Asp Arg Val Asn Val Ala Asp Phe Arg Lys 20 25 30 Leu Glu TrpLeu Phe Pro Glu Thr Thr Ala Asn Phe Asp Lys Leu Leu 35 40 45 Ile Gln TyrArg Gly Phe Cys Ala Tyr Thr Phe Ala Ala Thr Asp Gly 50 55 60 Leu Leu LeuPro Gly Asn Pro Ala Ile Gly Ile Leu Lys Tyr Lys Glu 65 70 75 80 Lys TyrTyr Thr Phe Asn Ser Lys Asp Ala Ala Tyr Ser Phe Ala Glu 85 90 95 Asn ProGlu His Tyr Ile Asp Ile Val Arg Glu Lys Ala Lys Lys Asn 100 105 110 ThrGlu Leu Ile Gln Leu Leu Glu Leu His Gln Gln Phe Glu Thr Phe 115 120 125Ile Pro Tyr Ser Gln Met Arg Asp Ala Asp Lys His Tyr Ile Lys Pro 130 135140 Ile Thr Lys Cys Glu Ser Ser Thr Gln Thr Asn Thr His Ile Leu Pro 145150 155 160 Pro Thr Ile Val Arg Ser Tyr Glu Trp Asn Glu Trp Glu Leu ArgArg 165 170 175 Lys Ala Ile Lys Leu Ala Asn Leu Arg Gln Lys Val Thr HisSer Val 180 185 190 Gln Thr Asp Leu Ser His Leu Arg Arg Glu Asn Cys SerGln Val Tyr 195 200 205 Pro Pro Lys Asp Thr Ser Thr Gln Ser Met Arg GluAsp Ser Thr Gly 210 215 220 Val Pro Arg Pro Gln Ile Tyr Leu Ala Gly LeuArg Gly Gly Lys Ser 225 230 235 240 Glu Ile Thr Asp Glu Val Lys Val AsnLeu Thr Arg Asp Val Asp Glu 245 250 255 Thr 65 344 DNA Homo sapiens CDS(9)..(296) 65 gtgatgat atg gcg aca aca aat ttt aat ctg cga ctt gag caagat ttg 50 Met Ala Thr Thr Asn Phe Asn Leu Arg Leu Glu Gln Asp Leu 1 510 cgt gat cgg gca ttt cca gtg ttt gag cgt tat gga ctg agc gca tca 98Arg Asp Arg Ala Phe Pro Val Phe Glu Arg Tyr Gly Leu Ser Ala Ser 15 20 2530 caa gcc ttt aaa ttg ttt tta aca caa gtt gct gag acc aat aaa att 146Gln Ala Phe Lys Leu Phe Leu Thr Gln Val Ala Glu Thr Asn Lys Ile 35 40 45ccc ttg tct ttt gat tat gca gag aca gag aat gtg ccg aat agt gtc 194 ProLeu Ser Phe Asp Tyr Ala Glu Thr Glu Asn Val Pro Asn Ser Val 50 55 60 acaaga aaa gca ttg act gaa gca aaa aat aga act gat ttt tca gat 242 Thr ArgLys Ala Leu Thr Glu Ala Lys Asn Arg Thr Asp Phe Ser Asp 65 70 75 gct tatgaa aca cct gaa gaa ttt atg aaa gcg atg caa gaa tta gcc 290 Ala Tyr GluThr Pro Glu Glu Phe Met Lys Ala Met Gln Glu Leu Ala 80 85 90 aat gcgtaagatatta gctgaaagcc aatttaagag agatattaaa aagcaatt 344 Asn Ala 95 6696 PRT Homo sapiens 66 Met Ala Thr Thr Asn Phe Asn Leu Arg Leu Glu GlnAsp Leu Arg Asp 1 5 10 15 Arg Ala Phe Pro Val Phe Glu Arg Tyr Gly LeuSer Ala Ser Gln Ala 20 25 30 Phe Lys Leu Phe Leu Thr Gln Val Ala Glu ThrAsn Lys Ile Pro Leu 35 40 45 Ser Phe Asp Tyr Ala Glu Thr Glu Asn Val ProAsn Ser Val Thr Arg 50 55 60 Lys Ala Leu Thr Glu Ala Lys Asn Arg Thr AspPhe Ser Asp Ala Tyr 65 70 75 80 Glu Thr Pro Glu Glu Phe Met Lys Ala MetGln Glu Leu Ala Asn Ala 85 90 95 67 445 DNA Homo sapiens CDS (26)..(409)67 gattaaattt cctctattgc ttggt atg gtg ctg ttc tgg gaa cag aca aaa 52Met Val Leu Phe Trp Glu Gln Thr Lys 1 5 tca ctt cac tgt ctt caa gta caacag gac ttc agc cag agc cgc acc 100 Ser Leu His Cys Leu Gln Val Gln GlnAsp Phe Ser Gln Ser Arg Thr 10 15 20 25 atc ccc agc cgc acc gtg gcc atcagc gac gct gca cag tta cct cat 148 Ile Pro Ser Arg Thr Val Ala Ile SerAsp Ala Ala Gln Leu Pro His 30 35 40 gac tac tgc acc aca cag ggg ggc actctt ctc acc aca cgg gga gga 196 Asp Tyr Cys Thr Thr Gln Gly Gly Thr LeuLeu Thr Thr Arg Gly Gly 45 50 55 act caa atc ttt tat gat aga aag ttt ctgttg gat tat tgc aat tct 244 Thr Gln Ile Phe Tyr Asp Arg Lys Phe Leu LeuAsp Tyr Cys Asn Ser 60 65 70 ccc atg gtt cag acc cca ccc tgc cat cta ccaaat atc cca gaa gtc 292 Pro Met Val Gln Thr Pro Pro Cys His Leu Pro AsnIle Pro Glu Val 75 80 85 act agc cct ggc acc tta atc gaa gac tcc aga gtagaa gta aac aat 340 Thr Ser Pro Gly Thr Leu Ile Glu Asp Ser Arg Val GluVal Asn Asn 90 95 100 105 ttg aac aac ata aac aat cat gag agg aaa cacgca gtt ggg gat gat 388 Leu Asn Asn Ile Asn Asn His Glu Arg Lys His AlaVal Gly Asp Asp 110 115 120 gct cag ttt gag atg ggc atc tgactctcctgcaaggatta gaagaaaagc 439 Ala Gln Phe Glu Met Gly Ile 125 agcaat 445 68128 PRT Homo sapiens 68 Met Val Leu Phe Trp Glu Gln Thr Lys Ser Leu HisCys Leu Gln Val 1 5 10 15 Gln Gln Asp Phe Ser Gln Ser Arg Thr Ile ProSer Arg Thr Val Ala 20 25 30 Ile Ser Asp Ala Ala Gln Leu Pro His Asp TyrCys Thr Thr Gln Gly 35 40 45 Gly Thr Leu Leu Thr Thr Arg Gly Gly Thr GlnIle Phe Tyr Asp Arg 50 55 60 Lys Phe Leu Leu Asp Tyr Cys Asn Ser Pro MetVal Gln Thr Pro Pro 65 70 75 80 Cys His Leu Pro Asn Ile Pro Glu Val ThrSer Pro Gly Thr Leu Ile 85 90 95 Glu Asp Ser Arg Val Glu Val Asn Asn LeuAsn Asn Ile Asn Asn His 100 105 110 Glu Arg Lys His Ala Val Gly Asp AspAla Gln Phe Glu Met Gly Ile 115 120 125 69 552 DNA Homo sapiens CDS(31)..(525) 69 tccaggcaac gctgcggctc cgcccacgtc atg gcg ccc gag gag aacgcg ggg 54 Met Ala Pro Glu Glu Asn Ala Gly 1 5 aca gaa ctc tgg ctg cagggt ttc gag cgc cgc ttc ctg gcg gcg cgc 102 Thr Glu Leu Trp Leu Gln GlyPhe Glu Arg Arg Phe Leu Ala Ala Arg 10 15 20 tca ctg cgc tcc ttc ccc tggcag agc tta gag gca aag tta aga gac 150 Ser Leu Arg Ser Phe Pro Trp GlnSer Leu Glu Ala Lys Leu Arg Asp 25 30 35 40 tca tca gat tct gag ctg ctgcgg gat att ttg cag aag acg agg gct 198 Ser Ser Asp Ser Glu Leu Leu ArgAsp Ile Leu Gln Lys Thr Arg Ala 45 50 55 gtc cac acg gag cct ttg gac gagctg tac gag gtg ctg gcg gag act 246 Val His Thr Glu Pro Leu Asp Glu LeuTyr Glu Val Leu Ala Glu Thr 60 65 70 ctg atg gcc aag gag tcc acc cag ggccac cgg agc tat ttg ctg acg 294 Leu Met Ala Lys Glu Ser Thr Gln Gly HisArg Ser Tyr Leu Leu Thr 75 80 85 tgc tgt att gcc cag aag cca tcg tgt cactgg tcg ggg tcc tgc gga 342 Cys Cys Ile Ala Gln Lys Pro Ser Cys His TrpSer Gly Ser Cys Gly 90 95 100 ggc tgg ctg cct gcc ggg agc aca agc aggctc ctg agg tct acc tgg 390 Gly Trp Leu Pro Ala Gly Ser Thr Ser Arg LeuLeu Arg Ser Thr Trp 105 110 115 120 cct tta ccg tcc gca acc cag aga cgtgcc agc tgt tca cca ccg agc 438 Pro Leu Pro Ser Ala Thr Gln Arg Arg AlaSer Cys Ser Pro Pro Ser 125 130 135 cag gct gga ctg gga tca gat ggg aagtgg aag ctc atc atg acc aga 486 Gln Ala Gly Leu Gly Ser Asp Gly Lys TrpLys Leu Ile Met Thr Arg 140 145 150 aac tgt ttc cct aca gag agc act tggaga tgg caa tgc tgaacctcac 535 Asn Cys Phe Pro Thr Glu Ser Thr Trp ArgTrp Gln Cys 155 160 165 actgtaggac tcacaca 552 70 165 PRT Homo sapiens70 Met Ala Pro Glu Glu Asn Ala Gly Thr Glu Leu Trp Leu Gln Gly Phe 1 510 15 Glu Arg Arg Phe Leu Ala Ala Arg Ser Leu Arg Ser Phe Pro Trp Gln 2025 30 Ser Leu Glu Ala Lys Leu Arg Asp Ser Ser Asp Ser Glu Leu Leu Arg 3540 45 Asp Ile Leu Gln Lys Thr Arg Ala Val His Thr Glu Pro Leu Asp Glu 5055 60 Leu Tyr Glu Val Leu Ala Glu Thr Leu Met Ala Lys Glu Ser Thr Gln 6570 75 80 Gly His Arg Ser Tyr Leu Leu Thr Cys Cys Ile Ala Gln Lys Pro Ser85 90 95 Cys His Trp Ser Gly Ser Cys Gly Gly Trp Leu Pro Ala Gly Ser Thr100 105 110 Ser Arg Leu Leu Arg Ser Thr Trp Pro Leu Pro Ser Ala Thr GlnArg 115 120 125 Arg Ala Ser Cys Ser Pro Pro Ser Gln Ala Gly Leu Gly SerAsp Gly 130 135 140 Lys Trp Lys Leu Ile Met Thr Arg Asn Cys Phe Pro ThrGlu Ser Thr 145 150 155 160 Trp Arg Trp Gln Cys 165 71 1411 DNA Homosapiens CDS (26)..(700) 71 ttctgatcat gtcactggca aggca atg ctt acg tcactt ggc ctg aag ttg 52 Met Leu Thr Ser Leu Gly Leu Lys Leu 1 5 ggg gatcgt gtt gtt att gca gga cag aag gtt ggt aca tta aga ttt 100 Gly Asp ArgVal Val Ile Ala Gly Gln Lys Val Gly Thr Leu Arg Phe 10 15 20 25 tgt ggaaca act gaa ttt gca agt ggg cag tgg gct ggc att gaa ctg 148 Cys Gly ThrThr Glu Phe Ala Ser Gly Gln Trp Ala Gly Ile Glu Leu 30 35 40 gat gaa ccagaa gga aaa aat aat gga agt gtt gga aaa gtc cag tac 196 Asp Glu Pro GluGly Lys Asn Asn Gly Ser Val Gly Lys Val Gln Tyr 45 50 55 ttt aaa tgt gccccc aag tat ggt att ttt gca cct ctt tca aag ata 244 Phe Lys Cys Ala ProLys Tyr Gly Ile Phe Ala Pro Leu Ser Lys Ile 60 65 70 agt aaa gca aaa ggtcga agg aag aat ata aca cac act cct tct aca 292 Ser Lys Ala Lys Gly ArgArg Lys Asn Ile Thr His Thr Pro Ser Thr 75 80 85 aaa gct gct gta cct ctcatc agg tcc cag aaa att gac gta gct cat 340 Lys Ala Ala Val Pro Leu IleArg Ser Gln Lys Ile Asp Val Ala His 90 95 100 105 gtg acg tca aaa gtaaat act gga tta atg aca tca aaa aaa gat agt 388 Val Thr Ser Lys Val AsnThr Gly Leu Met Thr Ser Lys Lys Asp Ser 110 115 120 gct tct gag tca acactt tca ttg cct cct ggt gaa gaa ctt aaa act 436 Ala Ser Glu Ser Thr LeuSer Leu Pro Pro Gly Glu Glu Leu Lys Thr 125 130 135 gtg aca gag aaa gatgtt gcc ctg ctt gga tct gtc agc agc tgc tcc 484 Val Thr Glu Lys Asp ValAla Leu Leu Gly Ser Val Ser Ser Cys Ser 140 145 150 tct aca tct tct ttggaa cac aga cag agc tac ccc aag aaa cag aat 532 Ser Thr Ser Ser Leu GluHis Arg Gln Ser Tyr Pro Lys Lys Gln Asn 155 160 165 gca atc agc agt aacaag aag aca atg agc aaa agc cct tcc ctt tca 580 Ala Ile Ser Ser Asn LysLys Thr Met Ser Lys Ser Pro Ser Leu Ser 170 175 180 185 tcc aga gcc agtgct ggt ttg aat tcc tca gca aca tct aca gca aat 628 Ser Arg Ala Ser AlaGly Leu Asn Ser Ser Ala Thr Ser Thr Ala Asn 190 195 200 aat agc cgt tgcgag ggg gaa ctc cgc ctc ggg aga gag agt gtt agt 676 Asn Ser Arg Cys GluGly Glu Leu Arg Leu Gly Arg Glu Ser Val Ser 205 210 215 ggt agg aca gagact ggg cac cat taggttcttt gggacaacaa acttcgctcc 730 Gly Arg Thr Glu ThrGly His His 220 225 aggatattgg tatggtatag agcttgaaaa accccatggcaagaatgatg gttcagttgg 790 aggtgtgcag tattttagct gttctccaag atatggaatatttgctcccc catccagggt 850 gcaaagagta acagattccc tggataccct ttcagaaatttcttcaaata aacagaacca 910 ttcttatcct ggttttagga gaagttttag cacaacttctgcttcttccc aaaaggagat 970 taacagaaga aatgcttttt ccaaatcgaa agctgctttgcgtcgcagtt ggagcagcac 1030 ccccaccgca ggtggcattg aagggagcgt gaagctgcacgaggggtctc aggtcctgct 1090 cacgagctcc aatgagatgg gtactgttag gtatgtgggccccactgact ttgcttcagg 1150 tatctggctt ggacttgagc tccgaagcgc caagggaaaaaatgatgggt cagtgggtga 1210 caagcgctat ttcacctgta agccgaacca tggagtcttagttcgaccga gcagagtgac 1270 ctatcgggga attaatgggt caaaacttgt ggatgagaattgttaagctt ctaaaatatt 1330 aaataagctc aaatatatat atttggtgta aataaagagtccatggtaaa tggtttactt 1390 tatttagcca tattaaaatt t 1411 72 225 PRT Homosapiens 72 Met Leu Thr Ser Leu Gly Leu Lys Leu Gly Asp Arg Val Val IleAla 1 5 10 15 Gly Gln Lys Val Gly Thr Leu Arg Phe Cys Gly Thr Thr GluPhe Ala 20 25 30 Ser Gly Gln Trp Ala Gly Ile Glu Leu Asp Glu Pro Glu GlyLys Asn 35 40 45 Asn Gly Ser Val Gly Lys Val Gln Tyr Phe Lys Cys Ala ProLys Tyr 50 55 60 Gly Ile Phe Ala Pro Leu Ser Lys Ile Ser Lys Ala Lys GlyArg Arg 65 70 75 80 Lys Asn Ile Thr His Thr Pro Ser Thr Lys Ala Ala ValPro Leu Ile 85 90 95 Arg Ser Gln Lys Ile Asp Val Ala His Val Thr Ser LysVal Asn Thr 100 105 110 Gly Leu Met Thr Ser Lys Lys Asp Ser Ala Ser GluSer Thr Leu Ser 115 120 125 Leu Pro Pro Gly Glu Glu Leu Lys Thr Val ThrGlu Lys Asp Val Ala 130 135 140 Leu Leu Gly Ser Val Ser Ser Cys Ser SerThr Ser Ser Leu Glu His 145 150 155 160 Arg Gln Ser Tyr Pro Lys Lys GlnAsn Ala Ile Ser Ser Asn Lys Lys 165 170 175 Thr Met Ser Lys Ser Pro SerLeu Ser Ser Arg Ala Ser Ala Gly Leu 180 185 190 Asn Ser Ser Ala Thr SerThr Ala Asn Asn Ser Arg Cys Glu Gly Glu 195 200 205 Leu Arg Leu Gly ArgGlu Ser Val Ser Gly Arg Thr Glu Thr Gly His 210 215 220 His 225 73 3974DNA Homo sapiens CDS (261)..(3656) 73 ggttcctgag cacttacttg cacagagattcaatgatgga ggtatcagcc ccaccatagg 60 aagctgaaat agtagtttcc ttcatatttctggacagccc ctctgtgggt gcaagaacat 120 tccctgacaa aggtgcagcc tccatatgaaatctgatctt ggtctgagac aatgtcttct 180 gcccagtttc actggatgac tcttgtcccctttttgtcct gccccctatc caggtcgttt 240 tctgatgtga cggctgagac atg aga tcttca gcc tcc agg ctc tcc agt ttt 293 Met Arg Ser Ser Ala Ser Arg Leu SerSer Phe 1 5 10 tcg tcg aga gat tca cta tgg aat cgg atg ccg gac cag atctct gtc 341 Ser Ser Arg Asp Ser Leu Trp Asn Arg Met Pro Asp Gln Ile SerVal 15 20 25 tcg gag ttc atc gcc gag acc acc gag gac tac aac tcg ccc accacg 389 Ser Glu Phe Ile Ala Glu Thr Thr Glu Asp Tyr Asn Ser Pro Thr Thr30 35 40 tcc agc ttc acc acg cgg ctg cac aac tgc agg aac acc gtc acg ctg437 Ser Ser Phe Thr Thr Arg Leu His Asn Cys Arg Asn Thr Val Thr Leu 4550 55 ctg gag gag gct cta ggc caa gat aga aca gcc ctt cag aaa gtg aag485 Leu Glu Glu Ala Leu Gly Gln Asp Arg Thr Ala Leu Gln Lys Val Lys 6065 70 75 aag tct gta aaa gca ata tat aat tct ggt caa gat cat gta caa aat533 Lys Ser Val Lys Ala Ile Tyr Asn Ser Gly Gln Asp His Val Gln Asn 8085 90 gaa gaa aac tat gca caa gtt ctt gat aag ttt ggg agt aat ttt tta581 Glu Glu Asn Tyr Ala Gln Val Leu Asp Lys Phe Gly Ser Asn Phe Leu 95100 105 agt cga gac aac ccc gac ctt ggc acc gcg ttt gtc aag ttt tct act629 Ser Arg Asp Asn Pro Asp Leu Gly Thr Ala Phe Val Lys Phe Ser Thr 110115 120 ctt aca aag gaa ctg tcc aca ctg ctg aaa aat ctg ctc cag ggt ttg677 Leu Thr Lys Glu Leu Ser Thr Leu Leu Lys Asn Leu Leu Gln Gly Leu 125130 135 agc cac aat gtg atc ttc acc ttg gat tct ttg tta aaa gga gac cta725 Ser His Asn Val Ile Phe Thr Leu Asp Ser Leu Leu Lys Gly Asp Leu 140145 150 155 aag gga gtc aaa gga gat ctc aag aag cca ttt gac aaa gcc tggaaa 773 Lys Gly Val Lys Gly Asp Leu Lys Lys Pro Phe Asp Lys Ala Trp Lys160 165 170 gat tat gag aca aag ttt aca aaa att gag aaa gag aaa aga gagcac 821 Asp Tyr Glu Thr Lys Phe Thr Lys Ile Glu Lys Glu Lys Arg Glu His175 180 185 gca aaa caa cat ggg atg atc cgc aca gag ata aca gga gct gagatt 869 Ala Lys Gln His Gly Met Ile Arg Thr Glu Ile Thr Gly Ala Glu Ile190 195 200 gcg gaa gaa atg gag aag gaa agg cgc ctc ttt cag ctc caa atgtgt 917 Ala Glu Glu Met Glu Lys Glu Arg Arg Leu Phe Gln Leu Gln Met Cys205 210 215 gaa tat ctc att aaa gtt aat gaa atc aag acc aaa aag ggt gtggat 965 Glu Tyr Leu Ile Lys Val Asn Glu Ile Lys Thr Lys Lys Gly Val Asp220 225 230 235 ctg ctg cag aat ctt ata aag tat tac cat gca cag tgc aatttc ttt 1013 Leu Leu Gln Asn Leu Ile Lys Tyr Tyr His Ala Gln Cys Asn PhePhe 240 245 250 caa gat ggc ttg aaa aca gct gat aag ttg aaa cag tac attgaa aaa 1061 Gln Asp Gly Leu Lys Thr Ala Asp Lys Leu Lys Gln Tyr Ile GluLys 255 260 265 ctg gct gct gat tta tat aat ata aaa cag acc cag gat gaagaa aag 1109 Leu Ala Ala Asp Leu Tyr Asn Ile Lys Gln Thr Gln Asp Glu GluLys 270 275 280 aaa cag cta act gca ctc cga gac tta ata aaa tcc tct cttcaa ctg 1157 Lys Gln Leu Thr Ala Leu Arg Asp Leu Ile Lys Ser Ser Leu GlnLeu 285 290 295 gat cag aaa gaa tct agg aga gat tct cag agc cgg caa ggagga tac 1205 Asp Gln Lys Glu Ser Arg Arg Asp Ser Gln Ser Arg Gln Gly GlyTyr 300 305 310 315 agc atg cat cag ctc cag ggc aat aag gaa tat ggc agtgaa aag aag 1253 Ser Met His Gln Leu Gln Gly Asn Lys Glu Tyr Gly Ser GluLys Lys 320 325 330 ggg tac ctg cta aag aaa agt gac ggg atc cgg aaa gtatgg cag agg 1301 Gly Tyr Leu Leu Lys Lys Ser Asp Gly Ile Arg Lys Val TrpGln Arg 335 340 345 agg aag tgt tca gtc aag aat ggg att ctg acc atc tcacat gcc aca 1349 Arg Lys Cys Ser Val Lys Asn Gly Ile Leu Thr Ile Ser HisAla Thr 350 355 360 tct aac agg caa cca gcc aag ttg aac ctt ctc acc tgccaa gta aaa 1397 Ser Asn Arg Gln Pro Ala Lys Leu Asn Leu Leu Thr Cys GlnVal Lys 365 370 375 cct aat gcc gaa gac aaa aaa tct ttt gac ctg ata tcacat aat aga 1445 Pro Asn Ala Glu Asp Lys Lys Ser Phe Asp Leu Ile Ser HisAsn Arg 380 385 390 395 aca tat cac ttt cag gca gaa gat gag cag gat tatgta gca tgg ata 1493 Thr Tyr His Phe Gln Ala Glu Asp Glu Gln Asp Tyr ValAla Trp Ile 400 405 410 tca gta ttg aca aat agc aaa gaa gag gcc cta accatg gcc ttc cgt 1541 Ser Val Leu Thr Asn Ser Lys Glu Glu Ala Leu Thr MetAla Phe Arg 415 420 425 gga gag cag agt gcg gga gag aac agc ctg gaa gacctg aca aaa gcc 1589 Gly Glu Gln Ser Ala Gly Glu Asn Ser Leu Glu Asp LeuThr Lys Ala 430 435 440 att att gag gat gtc cag cgg ctc cca ggg aat gacatt tgc tgc gat 1637 Ile Ile Glu Asp Val Gln Arg Leu Pro Gly Asn Asp IleCys Cys Asp 445 450 455 tgt ggc tca tca gaa ccc acc tgg ctt tca acc aacttg ggt att ttg 1685 Cys Gly Ser Ser Glu Pro Thr Trp Leu Ser Thr Asn LeuGly Ile Leu 460 465 470 475 acc tgt ata gaa tgt tct ggc atc cat agg gaaatg ggg gtt cat att 1733 Thr Cys Ile Glu Cys Ser Gly Ile His Arg Glu MetGly Val His Ile 480 485 490 tct cgc att cag tct ttg gaa cta gac aaa ttagga act tct gaa ctc 1781 Ser Arg Ile Gln Ser Leu Glu Leu Asp Lys Leu GlyThr Ser Glu Leu 495 500 505 ttg ctg gcc aag aat gta gga aac aat agt tttaat gat att atg gaa 1829 Leu Leu Ala Lys Asn Val Gly Asn Asn Ser Phe AsnAsp Ile Met Glu 510 515 520 gca aat tta ccc agc ccc tca cca aaa ccc acccct tca agt gat atg 1877 Ala Asn Leu Pro Ser Pro Ser Pro Lys Pro Thr ProSer Ser Asp Met 525 530 535 act gta cga aaa gaa tat atc act gca aag tatgta gat cat agg ttt 1925 Thr Val Arg Lys Glu Tyr Ile Thr Ala Lys Tyr ValAsp His Arg Phe 540 545 550 555 tca agg aag acc tgt tca act tca tca gctaaa cta aat gaa ttg ctt 1973 Ser Arg Lys Thr Cys Ser Thr Ser Ser Ala LysLeu Asn Glu Leu Leu 560 565 570 gag gcc atc aaa tcc agg gat tta ctt gcacta att caa gtc tat gca 2021 Glu Ala Ile Lys Ser Arg Asp Leu Leu Ala LeuIle Gln Val Tyr Ala 575 580 585 gaa ggg gta gag cta atg gaa cca ctg ctggaa cct ggg cag gag ctt 2069 Glu Gly Val Glu Leu Met Glu Pro Leu Leu GluPro Gly Gln Glu Leu 590 595 600 ggg gag aca gcc ctt cac ctt gcc gtc cgaact gca gat cag aca tct 2117 Gly Glu Thr Ala Leu His Leu Ala Val Arg ThrAla Asp Gln Thr Ser 605 610 615 ctc cat ttg gtt gac ttc ctt gta caa aactgt ggg aac ctg gat aag 2165 Leu His Leu Val Asp Phe Leu Val Gln Asn CysGly Asn Leu Asp Lys 620 625 630 635 cag acg gcc ctg gga aac aca gtt ctacac tac tgt agt atg tac agt 2213 Gln Thr Ala Leu Gly Asn Thr Val Leu HisTyr Cys Ser Met Tyr Ser 640 645 650 aaa cct gag tgt ttg aag ctt ttg ctcagg agc aag ccc act gtg gat 2261 Lys Pro Glu Cys Leu Lys Leu Leu Leu ArgSer Lys Pro Thr Val Asp 655 660 665 ata gtt aac cag gct gga gaa act gcccta gac ata gca aag aga cta 2309 Ile Val Asn Gln Ala Gly Glu Thr Ala LeuAsp Ile Ala Lys Arg Leu 670 675 680 aaa gct acc cag tgt gaa gat ctg ctttcc cag gct aaa tct gga aag 2357 Lys Ala Thr Gln Cys Glu Asp Leu Leu SerGln Ala Lys Ser Gly Lys 685 690 695 ttc aat cca cac gtc cac gta gaa tatgag tgg aat ctt cga cag gag 2405 Phe Asn Pro His Val His Val Glu Tyr GluTrp Asn Leu Arg Gln Glu 700 705 710 715 gag ata gat gag agc gat gat gatctg gat gac aaa cca agc cct atc 2453 Glu Ile Asp Glu Ser Asp Asp Asp LeuAsp Asp Lys Pro Ser Pro Ile 720 725 730 aag aaa gag cgc tca ccc aga cctcag agc ttc tgc cac tcc tcc agc 2501 Lys Lys Glu Arg Ser Pro Arg Pro GlnSer Phe Cys His Ser Ser Ser 735 740 745 atc tcc ccc cag gac aag ctg gcactg cca gga ttc agc act cca agg 2549 Ile Ser Pro Gln Asp Lys Leu Ala LeuPro Gly Phe Ser Thr Pro Arg 750 755 760 gac aaa cag cgg ctc tcc tat ggagcc ttc acc aac cag atc ttc gtt 2597 Asp Lys Gln Arg Leu Ser Tyr Gly AlaPhe Thr Asn Gln Ile Phe Val 765 770 775 tcc aca agc aca gac tcg ccc acatca cca acc acg gag gct ccc cct 2645 Ser Thr Ser Thr Asp Ser Pro Thr SerPro Thr Thr Glu Ala Pro Pro 780 785 790 795 ctg ccc cct agg aac gcc gggaaa ggt cca act ggc cca cct tca aca 2693 Leu Pro Pro Arg Asn Ala Gly LysGly Pro Thr Gly Pro Pro Ser Thr 800 805 810 ctc cct cta agc acc cag acctct agt ggc agc tcc acc cta tcc aag 2741 Leu Pro Leu Ser Thr Gln Thr SerSer Gly Ser Ser Thr Leu Ser Lys 815 820 825 aag agg cct cct ccc cca ccaccc gga cac aag aga acc cta tcc gac 2789 Lys Arg Pro Pro Pro Pro Pro ProGly His Lys Arg Thr Leu Ser Asp 830 835 840 cct ccc agc cca cta cct catggg ccc cca aac aaa ggc gca gtt cct 2837 Pro Pro Ser Pro Leu Pro His GlyPro Pro Asn Lys Gly Ala Val Pro 845 850 855 tgg ggt aac gat ggg ggt ccatcc tct tca agt aag act aca aac aag 2885 Trp Gly Asn Asp Gly Gly Pro SerSer Ser Ser Lys Thr Thr Asn Lys 860 865 870 875 ttt gag gga cta tcc cagcag tcg agc acc agt tct gca aag act gcc 2933 Phe Glu Gly Leu Ser Gln GlnSer Ser Thr Ser Ser Ala Lys Thr Ala 880 885 890 ctt ggc cca aga gtt cttcct aaa cta cct cag aaa gtg gca cta agg 2981 Leu Gly Pro Arg Val Leu ProLys Leu Pro Gln Lys Val Ala Leu Arg 895 900 905 aaa aca gat cat ctc tcccta gac aaa gcc acc atc ccg ccc gaa atc 3029 Lys Thr Asp His Leu Ser LeuAsp Lys Ala Thr Ile Pro Pro Glu Ile 910 915 920 ttt cag aaa tca tca cagttg gca gag ttg cca caa aag cca cca cct 3077 Phe Gln Lys Ser Ser Gln LeuAla Glu Leu Pro Gln Lys Pro Pro Pro 925 930 935 gga gac ctg ccc cca aagccc aca gaa ctg gcc ccc aag ccc caa att 3125 Gly Asp Leu Pro Pro Lys ProThr Glu Leu Ala Pro Lys Pro Gln Ile 940 945 950 955 gga gat ttg ccg cctaag cca gga gaa ctg ccc ccc aaa cca cag ctg 3173 Gly Asp Leu Pro Pro LysPro Gly Glu Leu Pro Pro Lys Pro Gln Leu 960 965 970 ggg gac ctg cca cccaaa ccc caa ctc tca gac tta cct ccc aaa cca 3221 Gly Asp Leu Pro Pro LysPro Gln Leu Ser Asp Leu Pro Pro Lys Pro 975 980 985 cag atg aag gac ctgccc ccc aaa cca cag ctg gga gac ctg cta gca 3269 Gln Met Lys Asp Leu ProPro Lys Pro Gln Leu Gly Asp Leu Leu Ala 990 995 1000 aaa tcc cag act ggagat gtc tca ccc aag gct cag caa ccc tct gag 3317 Lys Ser Gln Thr Gly AspVal Ser Pro Lys Ala Gln Gln Pro Ser Glu 1005 1010 1015 gtc aca ctg aagtca cac cca ttg gat cta tcc cca aat gtg cag tcc 3365 Val Thr Leu Lys SerHis Pro Leu Asp Leu Ser Pro Asn Val Gln Ser 1020 1025 1030 1035 aga gacgcc atc caa aag caa gca tct gaa gac tcc aac gac ctc acg 3413 Arg Asp AlaIle Gln Lys Gln Ala Ser Glu Asp Ser Asn Asp Leu Thr 1040 1045 1050 cctact ctg cca gag acg ccc gta cca ctg ccc aga aaa atc aat acg 3461 Pro ThrLeu Pro Glu Thr Pro Val Pro Leu Pro Arg Lys Ile Asn Thr 1055 1060 1065ggg aaa aat aaa gtg agg cga gtg aag acc att tat gac tgc cag gca 3509 GlyLys Asn Lys Val Arg Arg Val Lys Thr Ile Tyr Asp Cys Gln Ala 1070 10751080 gac aac gat gac gag ctc aca ttc atc gag gga gaa gtg att atc gtc3557 Asp Asn Asp Asp Glu Leu Thr Phe Ile Glu Gly Glu Val Ile Ile Val1085 1090 1095 aca ggg gaa gag gac cag gag tgg tgg att ggc cac atc gaagga cag 3605 Thr Gly Glu Glu Asp Gln Glu Trp Trp Ile Gly His Ile Glu GlyGln 1100 1105 1110 1115 cct gaa agg aag ggg gtc ttt cca gtg tcc ttt gttcat atc ctg tct 3653 Pro Glu Arg Lys Gly Val Phe Pro Val Ser Phe Val HisIle Leu Ser 1120 1125 1130 gac tagcaaaacg cagaacctta agattgtccacatccttcat gcaagactgc 3706 Asp tgccttcatg taaccctggg cacagtgtgtatatagctgc tgttacagag taagaaactc 3766 atggaagggc cacctcagga gggggatataatgtgtgttg taaatatcct gtggttttct 3826 gccttcacca gtatgagggt agcctcggacccggcgcgcc ttactggttt gccaaagcca 3886 tccttggcat ctagcactta catctctctatgctgttcta caagcaaaca aacaaaaata 3946 ggagtatagg aactgctggc tttgcaaa3974 74 1132 PRT Homo sapiens 74 Met Arg Ser Ser Ala Ser Arg Leu Ser SerPhe Ser Ser Arg Asp Ser 1 5 10 15 Leu Trp Asn Arg Met Pro Asp Gln IleSer Val Ser Glu Phe Ile Ala 20 25 30 Glu Thr Thr Glu Asp Tyr Asn Ser ProThr Thr Ser Ser Phe Thr Thr 35 40 45 Arg Leu His Asn Cys Arg Asn Thr ValThr Leu Leu Glu Glu Ala Leu 50 55 60 Gly Gln Asp Arg Thr Ala Leu Gln LysVal Lys Lys Ser Val Lys Ala 65 70 75 80 Ile Tyr Asn Ser Gly Gln Asp HisVal Gln Asn Glu Glu Asn Tyr Ala 85 90 95 Gln Val Leu Asp Lys Phe Gly SerAsn Phe Leu Ser Arg Asp Asn Pro 100 105 110 Asp Leu Gly Thr Ala Phe ValLys Phe Ser Thr Leu Thr Lys Glu Leu 115 120 125 Ser Thr Leu Leu Lys AsnLeu Leu Gln Gly Leu Ser His Asn Val Ile 130 135 140 Phe Thr Leu Asp SerLeu Leu Lys Gly Asp Leu Lys Gly Val Lys Gly 145 150 155 160 Asp Leu LysLys Pro Phe Asp Lys Ala Trp Lys Asp Tyr Glu Thr Lys 165 170 175 Phe ThrLys Ile Glu Lys Glu Lys Arg Glu His Ala Lys Gln His Gly 180 185 190 MetIle Arg Thr Glu Ile Thr Gly Ala Glu Ile Ala Glu Glu Met Glu 195 200 205Lys Glu Arg Arg Leu Phe Gln Leu Gln Met Cys Glu Tyr Leu Ile Lys 210 215220 Val Asn Glu Ile Lys Thr Lys Lys Gly Val Asp Leu Leu Gln Asn Leu 225230 235 240 Ile Lys Tyr Tyr His Ala Gln Cys Asn Phe Phe Gln Asp Gly LeuLys 245 250 255 Thr Ala Asp Lys Leu Lys Gln Tyr Ile Glu Lys Leu Ala AlaAsp Leu 260 265 270 Tyr Asn Ile Lys Gln Thr Gln Asp Glu Glu Lys Lys GlnLeu Thr Ala 275 280 285 Leu Arg Asp Leu Ile Lys Ser Ser Leu Gln Leu AspGln Lys Glu Ser 290 295 300 Arg Arg Asp Ser Gln Ser Arg Gln Gly Gly TyrSer Met His Gln Leu 305 310 315 320 Gln Gly Asn Lys Glu Tyr Gly Ser GluLys Lys Gly Tyr Leu Leu Lys 325 330 335 Lys Ser Asp Gly Ile Arg Lys ValTrp Gln Arg Arg Lys Cys Ser Val 340 345 350 Lys Asn Gly Ile Leu Thr IleSer His Ala Thr Ser Asn Arg Gln Pro 355 360 365 Ala Lys Leu Asn Leu LeuThr Cys Gln Val Lys Pro Asn Ala Glu Asp 370 375 380 Lys Lys Ser Phe AspLeu Ile Ser His Asn Arg Thr Tyr His Phe Gln 385 390 395 400 Ala Glu AspGlu Gln Asp Tyr Val Ala Trp Ile Ser Val Leu Thr Asn 405 410 415 Ser LysGlu Glu Ala Leu Thr Met Ala Phe Arg Gly Glu Gln Ser Ala 420 425 430 GlyGlu Asn Ser Leu Glu Asp Leu Thr Lys Ala Ile Ile Glu Asp Val 435 440 445Gln Arg Leu Pro Gly Asn Asp Ile Cys Cys Asp Cys Gly Ser Ser Glu 450 455460 Pro Thr Trp Leu Ser Thr Asn Leu Gly Ile Leu Thr Cys Ile Glu Cys 465470 475 480 Ser Gly Ile His Arg Glu Met Gly Val His Ile Ser Arg Ile GlnSer 485 490 495 Leu Glu Leu Asp Lys Leu Gly Thr Ser Glu Leu Leu Leu AlaLys Asn 500 505 510 Val Gly Asn Asn Ser Phe Asn Asp Ile Met Glu Ala AsnLeu Pro Ser 515 520 525 Pro Ser Pro Lys Pro Thr Pro Ser Ser Asp Met ThrVal Arg Lys Glu 530 535 540 Tyr Ile Thr Ala Lys Tyr Val Asp His Arg PheSer Arg Lys Thr Cys 545 550 555 560 Ser Thr Ser Ser Ala Lys Leu Asn GluLeu Leu Glu Ala Ile Lys Ser 565 570 575 Arg Asp Leu Leu Ala Leu Ile GlnVal Tyr Ala Glu Gly Val Glu Leu 580 585 590 Met Glu Pro Leu Leu Glu ProGly Gln Glu Leu Gly Glu Thr Ala Leu 595 600 605 His Leu Ala Val Arg ThrAla Asp Gln Thr Ser Leu His Leu Val Asp 610 615 620 Phe Leu Val Gln AsnCys Gly Asn Leu Asp Lys Gln Thr Ala Leu Gly 625 630 635 640 Asn Thr ValLeu His Tyr Cys Ser Met Tyr Ser Lys Pro Glu Cys Leu 645 650 655 Lys LeuLeu Leu Arg Ser Lys Pro Thr Val Asp Ile Val Asn Gln Ala 660 665 670 GlyGlu Thr Ala Leu Asp Ile Ala Lys Arg Leu Lys Ala Thr Gln Cys 675 680 685Glu Asp Leu Leu Ser Gln Ala Lys Ser Gly Lys Phe Asn Pro His Val 690 695700 His Val Glu Tyr Glu Trp Asn Leu Arg Gln Glu Glu Ile Asp Glu Ser 705710 715 720 Asp Asp Asp Leu Asp Asp Lys Pro Ser Pro Ile Lys Lys Glu ArgSer 725 730 735 Pro Arg Pro Gln Ser Phe Cys His Ser Ser Ser Ile Ser ProGln Asp 740 745 750 Lys Leu Ala Leu Pro Gly Phe Ser Thr Pro Arg Asp LysGln Arg Leu 755 760 765 Ser Tyr Gly Ala Phe Thr Asn Gln Ile Phe Val SerThr Ser Thr Asp 770 775 780 Ser Pro Thr Ser Pro Thr Thr Glu Ala Pro ProLeu Pro Pro Arg Asn 785 790 795 800 Ala Gly Lys Gly Pro Thr Gly Pro ProSer Thr Leu Pro Leu Ser Thr 805 810 815 Gln Thr Ser Ser Gly Ser Ser ThrLeu Ser Lys Lys Arg Pro Pro Pro 820 825 830 Pro Pro Pro Gly His Lys ArgThr Leu Ser Asp Pro Pro Ser Pro Leu 835 840 845 Pro His Gly Pro Pro AsnLys Gly Ala Val Pro Trp Gly Asn Asp Gly 850 855 860 Gly Pro Ser Ser SerSer Lys Thr Thr Asn Lys Phe Glu Gly Leu Ser 865 870 875 880 Gln Gln SerSer Thr Ser Ser Ala Lys Thr Ala Leu Gly Pro Arg Val 885 890 895 Leu ProLys Leu Pro Gln Lys Val Ala Leu Arg Lys Thr Asp His Leu 900 905 910 SerLeu Asp Lys Ala Thr Ile Pro Pro Glu Ile Phe Gln Lys Ser Ser 915 920 925Gln Leu Ala Glu Leu Pro Gln Lys Pro Pro Pro Gly Asp Leu Pro Pro 930 935940 Lys Pro Thr Glu Leu Ala Pro Lys Pro Gln Ile Gly Asp Leu Pro Pro 945950 955 960 Lys Pro Gly Glu Leu Pro Pro Lys Pro Gln Leu Gly Asp Leu ProPro 965 970 975 Lys Pro Gln Leu Ser Asp Leu Pro Pro Lys Pro Gln Met LysAsp Leu 980 985 990 Pro Pro Lys Pro Gln Leu Gly Asp Leu Leu Ala Lys SerGln Thr Gly 995 1000 1005 Asp Val Ser Pro Lys Ala Gln Gln Pro Ser GluVal Thr Leu Lys Ser 1010 1015 1020 His Pro Leu Asp Leu Ser Pro Asn ValGln Ser Arg Asp Ala Ile Gln 1025 1030 1035 1040 Lys Gln Ala Ser Glu AspSer Asn Asp Leu Thr Pro Thr Leu Pro Glu 1045 1050 1055 Thr Pro Val ProLeu Pro Arg Lys Ile Asn Thr Gly Lys Asn Lys Val 1060 1065 1070 Arg ArgVal Lys Thr Ile Tyr Asp Cys Gln Ala Asp Asn Asp Asp Glu 1075 1080 1085Leu Thr Phe Ile Glu Gly Glu Val Ile Ile Val Thr Gly Glu Glu Asp 10901095 1100 Gln Glu Trp Trp Ile Gly His Ile Glu Gly Gln Pro Glu Arg LysGly 1105 1110 1115 1120 Val Phe Pro Val Ser Phe Val His Ile Leu Ser Asp1125 1130 75 1739 DNA Homo sapiens CDS (19)..(1680) 75 acctggccctacctaagc atg atc atg gaa agc aag ttc cgg gag aaa ctt 51 Met Ile Met GluSer Lys Phe Arg Glu Lys Leu 1 5 10 gag ccc aag atc cga gag aag agc atccac ctg agg acc ttt acc ttt 99 Glu Pro Lys Ile Arg Glu Lys Ser Ile HisLeu Arg Thr Phe Thr Phe 15 20 25 acc aag ctc tac ttt gga cag aag tgt cccagg gtc aac ggt gtc aag 147 Thr Lys Leu Tyr Phe Gly Gln Lys Cys Pro ArgVal Asn Gly Val Lys 30 35 40 gca cac act aat acg tgc aac cga aga cgt gtgact gtg gac ctg cag 195 Ala His Thr Asn Thr Cys Asn Arg Arg Arg Val ThrVal Asp Leu Gln 45 50 55 atc tgc ccc agc agc acc tgg gat gta agc agt gggggc tgc ttc tgt 243 Ile Cys Pro Ser Ser Thr Trp Asp Val Ser Ser Gly GlyCys Phe Cys 60 65 70 75 gtc ccc atg aaa gac acc tgg gca gag atg gga cagggg gac agc agg 291 Val Pro Met Lys Asp Thr Trp Ala Glu Met Gly Gln GlyAsp Ser Arg 80 85 90 ggt gga aaa gtg ggc agc gtg ttt acc aag agc ccc tccttt tca tct 339 Gly Gly Lys Val Gly Ser Val Phe Thr Lys Ser Pro Ser PheSer Ser 95 100 105 tca ggg tat cgt ggg gtg agc tac atc ggg gac tgt tatatc agt gtg 387 Ser Gly Tyr Arg Gly Val Ser Tyr Ile Gly Asp Cys Tyr IleSer Val 110 115 120 gag ctg cag aag att cat gct ggt gtg aac ggg atc caggtg ggt gga 435 Glu Leu Gln Lys Ile His Ala Gly Val Asn Gly Ile Gln ValGly Gly 125 130 135 gcc cgg cgg gtc atc ctg gag ccc ctc cta ttg gac aagccc ttt gtg 483 Ala Arg Arg Val Ile Leu Glu Pro Leu Leu Leu Asp Lys ProPhe Val 140 145 150 155 gga gcc gtg act gtg ttc ttc ctt cag aag ccg cctaat agc ttc cct 531 Gly Ala Val Thr Val Phe Phe Leu Gln Lys Pro Pro AsnSer Phe Pro 160 165 170 ctg ccc ctg aag cac cta cag atc aac tgg act ggcctg acc aac ctg 579 Leu Pro Leu Lys His Leu Gln Ile Asn Trp Thr Gly LeuThr Asn Leu 175 180 185 ctg gat gcg ccg gga atc aat gat gtg tca gac agctta ctg gag gac 627 Leu Asp Ala Pro Gly Ile Asn Asp Val Ser Asp Ser LeuLeu Glu Asp 190 195 200 ctc att gcc acc cac ctg gtg ctg ccc aac cgt gtgact gtg cct gtg 675 Leu Ile Ala Thr His Leu Val Leu Pro Asn Arg Val ThrVal Pro Val 205 210 215 aag aag ggg ctg gat ctg acc aac ctg cgc ttc cctctg ccc tgt ggg 723 Lys Lys Gly Leu Asp Leu Thr Asn Leu Arg Phe Pro LeuPro Cys Gly 220 225 230 235 gtg atc aga gtg cac ttg ctg gag gca gag cagctg gcc cag aag gac 771 Val Ile Arg Val His Leu Leu Glu Ala Glu Gln LeuAla Gln Lys Asp 240 245 250 aac ttt ctg ggg ctc cga ggc aag tca gat ccctac gcc aag gtg agc 819 Asn Phe Leu Gly Leu Arg Gly Lys Ser Asp Pro TyrAla Lys Val Ser 255 260 265 atc ggc cta cag cat ttc cgg agt agg acc atctac agg aac ctg aac 867 Ile Gly Leu Gln His Phe Arg Ser Arg Thr Ile TyrArg Asn Leu Asn 270 275 280 ccc acc tgg aac gaa gtg ttc cag ttc atg gtgtac gaa gtc cct gga 915 Pro Thr Trp Asn Glu Val Phe Gln Phe Met Val TyrGlu Val Pro Gly 285 290 295 cag gac ctg gag gta gac ctg tat gat gag gatacc gac agg gat gac 963 Gln Asp Leu Glu Val Asp Leu Tyr Asp Glu Asp ThrAsp Arg Asp Asp 300 305 310 315 ttc ctg ggc agc ctg cag atc tgc ctt ggagat gtc atg acc aac aga 1011 Phe Leu Gly Ser Leu Gln Ile Cys Leu Gly AspVal Met Thr Asn Arg 320 325 330 gtg gtg gat gag tgg ttt gtc ctg aat gacaca acc agc ggg cgg ctg 1059 Val Val Asp Glu Trp Phe Val Leu Asn Asp ThrThr Ser Gly Arg Leu 335 340 345 cac ctg cgg ctg gag tgg ctt tca ttg cttact gac caa gac gtt ctg 1107 His Leu Arg Leu Glu Trp Leu Ser Leu Leu ThrAsp Gln Asp Val Leu 350 355 360 act gag gac cat ggt ggc ctt tcc act gccatt ctc gtg gtc ttc ttg 1155 Thr Glu Asp His Gly Gly Leu Ser Thr Ala IleLeu Val Val Phe Leu 365 370 375 gag agt gcc tgc aac ttg ccg aga aac cctttt gac tac ctg aat ggt 1203 Glu Ser Ala Cys Asn Leu Pro Arg Asn Pro PheAsp Tyr Leu Asn Gly 380 385 390 395 gaa tat cga gcc aaa aaa ctc tcc aggttt gcc aga aac aag gtc agc 1251 Glu Tyr Arg Ala Lys Lys Leu Ser Arg PheAla Arg Asn Lys Val Ser 400 405 410 aaa gac cct tct tcc tat gtc aaa ctatct gta ggc aag aag aca cat 1299 Lys Asp Pro Ser Ser Tyr Val Lys Leu SerVal Gly Lys Lys Thr His 415 420 425 aca agt aag acc tgt ccc cac aac aaggac cct gtg tgg agc cag gtg 1347 Thr Ser Lys Thr Cys Pro His Asn Lys AspPro Val Trp Ser Gln Val 430 435 440 ttc tcc ttc ttt gtg cac aat gtg gccact gag cgg ctc cat ctg aag 1395 Phe Ser Phe Phe Val His Asn Val Ala ThrGlu Arg Leu His Leu Lys 445 450 455 gtg ctt gat gat gac cag gag tgt gctctg gga atg ctg gag gtc ccc 1443 Val Leu Asp Asp Asp Gln Glu Cys Ala LeuGly Met Leu Glu Val Pro 460 465 470 475 ctg tgc cag atc ctc ccc tat gctgac ctc act ctt gag cag cgc ttt 1491 Leu Cys Gln Ile Leu Pro Tyr Ala AspLeu Thr Leu Glu Gln Arg Phe 480 485 490 cag ctg gac cac tca ggc ctg gacagc ctc atc tcc atg agg ctg gtg 1539 Gln Leu Asp His Ser Gly Leu Asp SerLeu Ile Ser Met Arg Leu Val 495 500 505 ctt cgg gta aac cta aca cca tgtacc agc agt gga gct gat ccc tac 1587 Leu Arg Val Asn Leu Thr Pro Cys ThrSer Ser Gly Ala Asp Pro Tyr 510 515 520 gtc cgt gtc tac ttg ttg cca gaaagg aag tgg gca tgt cgt aag aag 1635 Val Arg Val Tyr Leu Leu Pro Glu ArgLys Trp Ala Cys Arg Lys Lys 525 530 535 act tca gtg aag cgg aag acc ttggaa ccc ctg ttt gat gag acg 1680 Thr Ser Val Lys Arg Lys Thr Leu Glu ProLeu Phe Asp Glu Thr 540 545 550 taagtgggct ggtggcctgc ctagagtgcctcacccattc aagtattttc caagtacct 1739 76 554 PRT Homo sapiens 76 Met IleMet Glu Ser Lys Phe Arg Glu Lys Leu Glu Pro Lys Ile Arg 1 5 10 15 GluLys Ser Ile His Leu Arg Thr Phe Thr Phe Thr Lys Leu Tyr Phe 20 25 30 GlyGln Lys Cys Pro Arg Val Asn Gly Val Lys Ala His Thr Asn Thr 35 40 45 CysAsn Arg Arg Arg Val Thr Val Asp Leu Gln Ile Cys Pro Ser Ser 50 55 60 ThrTrp Asp Val Ser Ser Gly Gly Cys Phe Cys Val Pro Met Lys Asp 65 70 75 80Thr Trp Ala Glu Met Gly Gln Gly Asp Ser Arg Gly Gly Lys Val Gly 85 90 95Ser Val Phe Thr Lys Ser Pro Ser Phe Ser Ser Ser Gly Tyr Arg Gly 100 105110 Val Ser Tyr Ile Gly Asp Cys Tyr Ile Ser Val Glu Leu Gln Lys Ile 115120 125 His Ala Gly Val Asn Gly Ile Gln Val Gly Gly Ala Arg Arg Val Ile130 135 140 Leu Glu Pro Leu Leu Leu Asp Lys Pro Phe Val Gly Ala Val ThrVal 145 150 155 160 Phe Phe Leu Gln Lys Pro Pro Asn Ser Phe Pro Leu ProLeu Lys His 165 170 175 Leu Gln Ile Asn Trp Thr Gly Leu Thr Asn Leu LeuAsp Ala Pro Gly 180 185 190 Ile Asn Asp Val Ser Asp Ser Leu Leu Glu AspLeu Ile Ala Thr His 195 200 205 Leu Val Leu Pro Asn Arg Val Thr Val ProVal Lys Lys Gly Leu Asp 210 215 220 Leu Thr Asn Leu Arg Phe Pro Leu ProCys Gly Val Ile Arg Val His 225 230 235 240 Leu Leu Glu Ala Glu Gln LeuAla Gln Lys Asp Asn Phe Leu Gly Leu 245 250 255 Arg Gly Lys Ser Asp ProTyr Ala Lys Val Ser Ile Gly Leu Gln His 260 265 270 Phe Arg Ser Arg ThrIle Tyr Arg Asn Leu Asn Pro Thr Trp Asn Glu 275 280 285 Val Phe Gln PheMet Val Tyr Glu Val Pro Gly Gln Asp Leu Glu Val 290 295 300 Asp Leu TyrAsp Glu Asp Thr Asp Arg Asp Asp Phe Leu Gly Ser Leu 305 310 315 320 GlnIle Cys Leu Gly Asp Val Met Thr Asn Arg Val Val Asp Glu Trp 325 330 335Phe Val Leu Asn Asp Thr Thr Ser Gly Arg Leu His Leu Arg Leu Glu 340 345350 Trp Leu Ser Leu Leu Thr Asp Gln Asp Val Leu Thr Glu Asp His Gly 355360 365 Gly Leu Ser Thr Ala Ile Leu Val Val Phe Leu Glu Ser Ala Cys Asn370 375 380 Leu Pro Arg Asn Pro Phe Asp Tyr Leu Asn Gly Glu Tyr Arg AlaLys 385 390 395 400 Lys Leu Ser Arg Phe Ala Arg Asn Lys Val Ser Lys AspPro Ser Ser 405 410 415 Tyr Val Lys Leu Ser Val Gly Lys Lys Thr His ThrSer Lys Thr Cys 420 425 430 Pro His Asn Lys Asp Pro Val Trp Ser Gln ValPhe Ser Phe Phe Val 435 440 445 His Asn Val Ala Thr Glu Arg Leu His LeuLys Val Leu Asp Asp Asp 450 455 460 Gln Glu Cys Ala Leu Gly Met Leu GluVal Pro Leu Cys Gln Ile Leu 465 470 475 480 Pro Tyr Ala Asp Leu Thr LeuGlu Gln Arg Phe Gln Leu Asp His Ser 485 490 495 Gly Leu Asp Ser Leu IleSer Met Arg Leu Val Leu Arg Val Asn Leu 500 505 510 Thr Pro Cys Thr SerSer Gly Ala Asp Pro Tyr Val Arg Val Tyr Leu 515 520 525 Leu Pro Glu ArgLys Trp Ala Cys Arg Lys Lys Thr Ser Val Lys Arg 530 535 540 Lys Thr LeuGlu Pro Leu Phe Asp Glu Thr 545 550 77 3084 DNA Homo sapiens CDS(61)..(2769) 77 gaccctctcc tgcagaggca gaggccgcct gccacaggcc acgcggagcagggtcccacc 60 atg gcc ctg agc atc ttg act gag cag ttc tgc atc cca aggcct cac 108 Met Ala Leu Ser Ile Leu Thr Glu Gln Phe Cys Ile Pro Arg ProHis 1 5 10 15 aag aag ccc ccg agc gcc cac agc atg aag gag gag gcc ttcctc cgg 156 Lys Lys Pro Pro Ser Ala His Ser Met Lys Glu Glu Ala Phe LeuArg 20 25 30 cgc cgc ttc tcc ctg tgt cca cct tcc tcc acc cct cag aaa gtcgac 204 Arg Arg Phe Ser Leu Cys Pro Pro Ser Ser Thr Pro Gln Lys Val Asp35 40 45 ccc cgg aag ctc acc cgg aac ttg ctc ctc agc gga gac aat gag ctc252 Pro Arg Lys Leu Thr Arg Asn Leu Leu Leu Ser Gly Asp Asn Glu Leu 5055 60 tac cca ctc agc cca ggg aag gac atg gag ccc aac ggc ccg tcg ctg300 Tyr Pro Leu Ser Pro Gly Lys Asp Met Glu Pro Asn Gly Pro Ser Leu 6570 75 80 ccc agg gat gaa ggg ccc ccg acc cca agc tct gcc acg aag gtg cca348 Pro Arg Asp Glu Gly Pro Pro Thr Pro Ser Ser Ala Thr Lys Val Pro 8590 95 ccg gca gag tac agg ctg tgc aac ggg tca gac aag gaa tgt gtg tcc396 Pro Ala Glu Tyr Arg Leu Cys Asn Gly Ser Asp Lys Glu Cys Val Ser 100105 110 ccc acc gcc agg gtc acc aag aag gag act ctc aag gcg cag aag gag444 Pro Thr Ala Arg Val Thr Lys Lys Glu Thr Leu Lys Ala Gln Lys Glu 115120 125 aac tac cgg cag gag aag aag cgc gcc aca cgg cag ctg ctc agc gct492 Asn Tyr Arg Gln Glu Lys Lys Arg Ala Thr Arg Gln Leu Leu Ser Ala 130135 140 ctg aca gac ccc agc gtg gtc atc atg gct gac agc ctg aag atc cgc540 Leu Thr Asp Pro Ser Val Val Ile Met Ala Asp Ser Leu Lys Ile Arg 145150 155 160 ggc acc ctg aag agc tgg acc aag ctg tgg tgc gtg ctg aag ccgggg 588 Gly Thr Leu Lys Ser Trp Thr Lys Leu Trp Cys Val Leu Lys Pro Gly165 170 175 gtg ctg ctc atc tac aag acg ccc aag gtg ggc cag tgg gtg ggcacg 636 Val Leu Leu Ile Tyr Lys Thr Pro Lys Val Gly Gln Trp Val Gly Thr180 185 190 gtg ctg ctg cac tgc tgc gag ctc atc gag cgg ccc tcc aag aaggac 684 Val Leu Leu His Cys Cys Glu Leu Ile Glu Arg Pro Ser Lys Lys Asp195 200 205 ggc ttc tgc ttc aag ctc ttc cac ccg ctg gat cag tcc gtc tgggcc 732 Gly Phe Cys Phe Lys Leu Phe His Pro Leu Asp Gln Ser Val Trp Ala210 215 220 gtg aag ggc ccc aaa ggt gag agc gtg ggc tcc atc aca cag cccctg 780 Val Lys Gly Pro Lys Gly Glu Ser Val Gly Ser Ile Thr Gln Pro Leu225 230 235 240 ccc agc agc tac ctg atc ttc agg gcc gcc tcc gag tca gatggt cgc 828 Pro Ser Ser Tyr Leu Ile Phe Arg Ala Ala Ser Glu Ser Asp GlyArg 245 250 255 tgc tgg ctg gac gcc ctg gag ctg gcc ctg cgc tgc tct agccta ctg 876 Cys Trp Leu Asp Ala Leu Glu Leu Ala Leu Arg Cys Ser Ser LeuLeu 260 265 270 aga ctg ggc acc tgc aag ccg ggc cga gac ggg gag cca gggacc tcg 924 Arg Leu Gly Thr Cys Lys Pro Gly Arg Asp Gly Glu Pro Gly ThrSer 275 280 285 cca gac gca tca ccc tca tcg ctc tgt ggg ctg cca gcc tcagcc act 972 Pro Asp Ala Ser Pro Ser Ser Leu Cys Gly Leu Pro Ala Ser AlaThr 290 295 300 gtc cac cca gac caa gac ctg ttc cca ctg aac ggg tct tccctg gag 1020 Val His Pro Asp Gln Asp Leu Phe Pro Leu Asn Gly Ser Ser LeuGlu 305 310 315 320 aac gat gca ttc tca gac aag tcg gag aga gag aac cctgag gag tca 1068 Asn Asp Ala Phe Ser Asp Lys Ser Glu Arg Glu Asn Pro GluGlu Ser 325 330 335 gat acc gag acc cag gac cat agc cgg aag acg gag agtggc agc gac 1116 Asp Thr Glu Thr Gln Asp His Ser Arg Lys Thr Glu Ser GlySer Asp 340 345 350 cag tca gag acc cct ggg gcc ccg gtg cgg aga ggg accacc tat gtg 1164 Gln Ser Glu Thr Pro Gly Ala Pro Val Arg Arg Gly Thr ThrTyr Val 355 360 365 gag cag gtc cag gag gag ctg ggg gag ctg ggc gag gcgtcc cag gtg 1212 Glu Gln Val Gln Glu Glu Leu Gly Glu Leu Gly Glu Ala SerGln Val 370 375 380 gag aca gtg tca gag gag aac aag agt ctg atg tgg accctg ctg aag 1260 Glu Thr Val Ser Glu Glu Asn Lys Ser Leu Met Trp Thr LeuLeu Lys 385 390 395 400 cag cta cgg cca ggc atg gac ctg tcc cgc gtg gtgcta ccc acg ttc 1308 Gln Leu Arg Pro Gly Met Asp Leu Ser Arg Val Val LeuPro Thr Phe 405 410 415 gta ctg gag ccg cgc tcc ttc ctg aac aag ctc tccgac tac tac tac 1356 Val Leu Glu Pro Arg Ser Phe Leu Asn Lys Leu Ser AspTyr Tyr Tyr 420 425 430 cac gca gac ctg ctc tcc agg gct gcg gtg gag gaggat gcc tac agc 1404 His Ala Asp Leu Leu Ser Arg Ala Ala Val Glu Glu AspAla Tyr Ser 435 440 445 cgc atg aag ctg gtg ctg cgg tgg tac ctg tct ggcttc tac aag aag 1452 Arg Met Lys Leu Val Leu Arg Trp Tyr Leu Ser Gly PheTyr Lys Lys 450 455 460 ccc aag gga atc aag aag ccg tac aac ccc atc ctgggg gag acc ttc 1500 Pro Lys Gly Ile Lys Lys Pro Tyr Asn Pro Ile Leu GlyGlu Thr Phe 465 470 475 480 cgc tgc tgc tgg ttc cac ccg cag act gac agccgc aca ttc tac ata 1548 Arg Cys Cys Trp Phe His Pro Gln Thr Asp Ser ArgThr Phe Tyr Ile 485 490 495 gca gag cag gtg tcc cac cac ccg ccc gtg tctgcc ttc cac gtc agc 1596 Ala Glu Gln Val Ser His His Pro Pro Val Ser AlaPhe His Val Ser 500 505 510 aac cgg aag gac ggc ttc tgc atc agt ggc agcatc aca gcc aag tcc 1644 Asn Arg Lys Asp Gly Phe Cys Ile Ser Gly Ser IleThr Ala Lys Ser 515 520 525 agg ttt tat ggg aac tcg ctg tcg gcg ctg ctggac ggc aaa gcc acg 1692 Arg Phe Tyr Gly Asn Ser Leu Ser Ala Leu Leu AspGly Lys Ala Thr 530 535 540 ctc acc ttc ctg aac cga gcc gag gat tac accctt acc atg ccc tac 1740 Leu Thr Phe Leu Asn Arg Ala Glu Asp Tyr Thr LeuThr Met Pro Tyr 545 550 555 560 gcc cac tgc aaa gga atc ctg tat ggc acgatg acc ctg gag ctg ggt 1788 Ala His Cys Lys Gly Ile Leu Tyr Gly Thr MetThr Leu Glu Leu Gly 565 570 575 ggg aag gtc acc atc gag tgt gcg aag aacaac ttc cag gcc cag ctg 1836 Gly Lys Val Thr Ile Glu Cys Ala Lys Asn AsnPhe Gln Ala Gln Leu 580 585 590 gaa ttc aaa ctc aag ccc ttc ttc ggg ggtagc acc agc atc aac cag 1884 Glu Phe Lys Leu Lys Pro Phe Phe Gly Gly SerThr Ser Ile Asn Gln 595 600 605 atc tcg gga aag atc acg tcg gga gag gaagtc ctg gcg agc ctc agt 1932 Ile Ser Gly Lys Ile Thr Ser Gly Glu Glu ValLeu Ala Ser Leu Ser 610 615 620 ggc cac tgg gac agg gac gtg ttt atc aaggag gaa ggg agc gga agc 1980 Gly His Trp Asp Arg Asp Val Phe Ile Lys GluGlu Gly Ser Gly Ser 625 630 635 640 agt gcg ctt ttc tgg acc ccg agc ggggag gtc cgc aga cag agg ctg 2028 Ser Ala Leu Phe Trp Thr Pro Ser Gly GluVal Arg Arg Gln Arg Leu 645 650 655 agg cag cac acg gtg ccg ctg gag gggcag acg gag ctg gag tcc gag 2076 Arg Gln His Thr Val Pro Leu Glu Gly GlnThr Glu Leu Glu Ser Glu 660 665 670 agg ctc tgg cag cac gtc acc agg gccatc agc aag ggc gac cag cac 2124 Arg Leu Trp Gln His Val Thr Arg Ala IleSer Lys Gly Asp Gln His 675 680 685 agg gcc aca cag gag aag ttt gca ctggag gag gca cag cgg cag cgg 2172 Arg Ala Thr Gln Glu Lys Phe Ala Leu GluGlu Ala Gln Arg Gln Arg 690 695 700 gcc cgt gag cgg cag gag agc ctc atgccc tgg aag ccg cag ctg ttc 2220 Ala Arg Glu Arg Gln Glu Ser Leu Met ProTrp Lys Pro Gln Leu Phe 705 710 715 720 cac ctg gac ccc atc acc cag gagtgg cac tac cga tac gag gac cac 2268 His Leu Asp Pro Ile Thr Gln Glu TrpHis Tyr Arg Tyr Glu Asp His 725 730 735 agc ccc tgg gac ccc ctg aag gacatc gcc cag ttt gag caa gac ggg 2316 Ser Pro Trp Asp Pro Leu Lys Asp IleAla Gln Phe Glu Gln Asp Gly 740 745 750 atc ctg cgg acc ttg cag cag gaggcc gtg gcc cgc cag acc acc ttc 2364 Ile Leu Arg Thr Leu Gln Gln Glu AlaVal Ala Arg Gln Thr Thr Phe 755 760 765 ctg ggc agc cca ggg ccc agg cacgag agg tct ggc cca gac cag cgg 2412 Leu Gly Ser Pro Gly Pro Arg His GluArg Ser Gly Pro Asp Gln Arg 770 775 780 ctt cgc aag gcc agc gac cag ccctcc ggc cac agc cag gcc acg gag 2460 Leu Arg Lys Ala Ser Asp Gln Pro SerGly His Ser Gln Ala Thr Glu 785 790 795 800 agc agc gga tcc acg cct gagtcc tgc cca gag ctc tca gac gag gag 2508 Ser Ser Gly Ser Thr Pro Glu SerCys Pro Glu Leu Ser Asp Glu Glu 805 810 815 cag gat ggt gac ttt gtc cctggc ggt gag agc cca tgc cct cgg tgc 2556 Gln Asp Gly Asp Phe Val Pro GlyGly Glu Ser Pro Cys Pro Arg Cys 820 825 830 agg aag gag gcg cgg cgg ctgcag gcc ctg cac gag gcc atc ctc tcc 2604 Arg Lys Glu Ala Arg Arg Leu GlnAla Leu His Glu Ala Ile Leu Ser 835 840 845 atc cga gag gcc cag cag gagctg cac agg cac ctc tcg gcc atg ctg 2652 Ile Arg Glu Ala Gln Gln Glu LeuHis Arg His Leu Ser Ala Met Leu 850 855 860 agc tcc acg gca cgg gca gcacag gca ccg acc cca ggc ctc ctg cag 2700 Ser Ser Thr Ala Arg Ala Ala GlnAla Pro Thr Pro Gly Leu Leu Gln 865 870 875 880 agc ccc cga tcc tgg ttcctg ctc tgc gtg ttc ctg gcg tgt cag ctg 2748 Ser Pro Arg Ser Trp Phe LeuLeu Cys Val Phe Leu Ala Cys Gln Leu 885 890 895 ttc att aac cac atc ctcaaa taggagccct gggggcagag ctcctggccg 2799 Phe Ile Asn His Ile Leu Lys900 gtcctgagcc ctccctccca ggcacccagc actttaagcc tgctccatgg aggcagagag2859 gcccggcaag cacagccact gtgacgggga gtccaggcgc aggagggacc cggggccaca2919 aggcgctgcg ggcccaggtg tgctgggccc ctctcagggg cactggcctc tctgcagggc2979 cttccgccca gcgctggcct taatgctaaa gccaaatgca gcttctgctg tgcgacgcac3039 tcctggccat cttgccgtgt caccccctgt ccggcctcca cttgc 3084 78 903 PRTHomo sapiens 78 Met Ala Leu Ser Ile Leu Thr Glu Gln Phe Cys Ile Pro ArgPro His 1 5 10 15 Lys Lys Pro Pro Ser Ala His Ser Met Lys Glu Glu AlaPhe Leu Arg 20 25 30 Arg Arg Phe Ser Leu Cys Pro Pro Ser Ser Thr Pro GlnLys Val Asp 35 40 45 Pro Arg Lys Leu Thr Arg Asn Leu Leu Leu Ser Gly AspAsn Glu Leu 50 55 60 Tyr Pro Leu Ser Pro Gly Lys Asp Met Glu Pro Asn GlyPro Ser Leu 65 70 75 80 Pro Arg Asp Glu Gly Pro Pro Thr Pro Ser Ser AlaThr Lys Val Pro 85 90 95 Pro Ala Glu Tyr Arg Leu Cys Asn Gly Ser Asp LysGlu Cys Val Ser 100 105 110 Pro Thr Ala Arg Val Thr Lys Lys Glu Thr LeuLys Ala Gln Lys Glu 115 120 125 Asn Tyr Arg Gln Glu Lys Lys Arg Ala ThrArg Gln Leu Leu Ser Ala 130 135 140 Leu Thr Asp Pro Ser Val Val Ile MetAla Asp Ser Leu Lys Ile Arg 145 150 155 160 Gly Thr Leu Lys Ser Trp ThrLys Leu Trp Cys Val Leu Lys Pro Gly 165 170 175 Val Leu Leu Ile Tyr LysThr Pro Lys Val Gly Gln Trp Val Gly Thr 180 185 190 Val Leu Leu His CysCys Glu Leu Ile Glu Arg Pro Ser Lys Lys Asp 195 200 205 Gly Phe Cys PheLys Leu Phe His Pro Leu Asp Gln Ser Val Trp Ala 210 215 220 Val Lys GlyPro Lys Gly Glu Ser Val Gly Ser Ile Thr Gln Pro Leu 225 230 235 240 ProSer Ser Tyr Leu Ile Phe Arg Ala Ala Ser Glu Ser Asp Gly Arg 245 250 255Cys Trp Leu Asp Ala Leu Glu Leu Ala Leu Arg Cys Ser Ser Leu Leu 260 265270 Arg Leu Gly Thr Cys Lys Pro Gly Arg Asp Gly Glu Pro Gly Thr Ser 275280 285 Pro Asp Ala Ser Pro Ser Ser Leu Cys Gly Leu Pro Ala Ser Ala Thr290 295 300 Val His Pro Asp Gln Asp Leu Phe Pro Leu Asn Gly Ser Ser LeuGlu 305 310 315 320 Asn Asp Ala Phe Ser Asp Lys Ser Glu Arg Glu Asn ProGlu Glu Ser 325 330 335 Asp Thr Glu Thr Gln Asp His Ser Arg Lys Thr GluSer Gly Ser Asp 340 345 350 Gln Ser Glu Thr Pro Gly Ala Pro Val Arg ArgGly Thr Thr Tyr Val 355 360 365 Glu Gln Val Gln Glu Glu Leu Gly Glu LeuGly Glu Ala Ser Gln Val 370 375 380 Glu Thr Val Ser Glu Glu Asn Lys SerLeu Met Trp Thr Leu Leu Lys 385 390 395 400 Gln Leu Arg Pro Gly Met AspLeu Ser Arg Val Val Leu Pro Thr Phe 405 410 415 Val Leu Glu Pro Arg SerPhe Leu Asn Lys Leu Ser Asp Tyr Tyr Tyr 420 425 430 His Ala Asp Leu LeuSer Arg Ala Ala Val Glu Glu Asp Ala Tyr Ser 435 440 445 Arg Met Lys LeuVal Leu Arg Trp Tyr Leu Ser Gly Phe Tyr Lys Lys 450 455 460 Pro Lys GlyIle Lys Lys Pro Tyr Asn Pro Ile Leu Gly Glu Thr Phe 465 470 475 480 ArgCys Cys Trp Phe His Pro Gln Thr Asp Ser Arg Thr Phe Tyr Ile 485 490 495Ala Glu Gln Val Ser His His Pro Pro Val Ser Ala Phe His Val Ser 500 505510 Asn Arg Lys Asp Gly Phe Cys Ile Ser Gly Ser Ile Thr Ala Lys Ser 515520 525 Arg Phe Tyr Gly Asn Ser Leu Ser Ala Leu Leu Asp Gly Lys Ala Thr530 535 540 Leu Thr Phe Leu Asn Arg Ala Glu Asp Tyr Thr Leu Thr Met ProTyr 545 550 555 560 Ala His Cys Lys Gly Ile Leu Tyr Gly Thr Met Thr LeuGlu Leu Gly 565 570 575 Gly Lys Val Thr Ile Glu Cys Ala Lys Asn Asn PheGln Ala Gln Leu 580 585 590 Glu Phe Lys Leu Lys Pro Phe Phe Gly Gly SerThr Ser Ile Asn Gln 595 600 605 Ile Ser Gly Lys Ile Thr Ser Gly Glu GluVal Leu Ala Ser Leu Ser 610 615 620 Gly His Trp Asp Arg Asp Val Phe IleLys Glu Glu Gly Ser Gly Ser 625 630 635 640 Ser Ala Leu Phe Trp Thr ProSer Gly Glu Val Arg Arg Gln Arg Leu 645 650 655 Arg Gln His Thr Val ProLeu Glu Gly Gln Thr Glu Leu Glu Ser Glu 660 665 670 Arg Leu Trp Gln HisVal Thr Arg Ala Ile Ser Lys Gly Asp Gln His 675 680 685 Arg Ala Thr GlnGlu Lys Phe Ala Leu Glu Glu Ala Gln Arg Gln Arg 690 695 700 Ala Arg GluArg Gln Glu Ser Leu Met Pro Trp Lys Pro Gln Leu Phe 705 710 715 720 HisLeu Asp Pro Ile Thr Gln Glu Trp His Tyr Arg Tyr Glu Asp His 725 730 735Ser Pro Trp Asp Pro Leu Lys Asp Ile Ala Gln Phe Glu Gln Asp Gly 740 745750 Ile Leu Arg Thr Leu Gln Gln Glu Ala Val Ala Arg Gln Thr Thr Phe 755760 765 Leu Gly Ser Pro Gly Pro Arg His Glu Arg Ser Gly Pro Asp Gln Arg770 775 780 Leu Arg Lys Ala Ser Asp Gln Pro Ser Gly His Ser Gln Ala ThrGlu 785 790 795 800 Ser Ser Gly Ser Thr Pro Glu Ser Cys Pro Glu Leu SerAsp Glu Glu 805 810 815 Gln Asp Gly Asp Phe Val Pro Gly Gly Glu Ser ProCys Pro Arg Cys 820 825 830 Arg Lys Glu Ala Arg Arg Leu Gln Ala Leu HisGlu Ala Ile Leu Ser 835 840 845 Ile Arg Glu Ala Gln Gln Glu Leu His ArgHis Leu Ser Ala Met Leu 850 855 860 Ser Ser Thr Ala Arg Ala Ala Gln AlaPro Thr Pro Gly Leu Leu Gln 865 870 875 880 Ser Pro Arg Ser Trp Phe LeuLeu Cys Val Phe Leu Ala Cys Gln Leu 885 890 895 Phe Ile Asn His Ile LeuLys 900 79 1905 DNA Homo sapiens CDS (73)..(1884) 79 gtcgacgcggccgcgctgcg tccagcattg gatatttgtc aggaatgcag ataccctgaa 60 gggaacacaa caatg gtc caa ggg ggt ttc cca gaa aaa atc aga caa aga 111 Met Val Gln GlyGly Phe Pro Glu Lys Ile Arg Gln Arg 1 5 10 tat gca gat ctg cct gga gaactg cac att att gaa ctt gaa aaa gat 159 Tyr Ala Asp Leu Pro Gly Glu LeuHis Ile Ile Glu Leu Glu Lys Asp 15 20 25 aag aat gga ctt gga ctc agc cttgct ggt aat aaa gac cga tca cgc 207 Lys Asn Gly Leu Gly Leu Ser Leu AlaGly Asn Lys Asp Arg Ser Arg 30 35 40 45 atg agc ata ttt gtg gtg gga attaac ccg gaa gga cct gct gcc gca 255 Met Ser Ile Phe Val Val Gly Ile AsnPro Glu Gly Pro Ala Ala Ala 50 55 60 gat gga cga atg cat att gga gat gaactc tta gag ata aac aat cag 303 Asp Gly Arg Met His Ile Gly Asp Glu LeuLeu Glu Ile Asn Asn Gln 65 70 75 att ctg tat gga aga agt cac caa aat gcatct gcc att att aag act 351 Ile Leu Tyr Gly Arg Ser His Gln Asn Ala SerAla Ile Ile Lys Thr 80 85 90 gcc cca tca aag gtc aag ctg gtt ttc atc agaaac gag gat gca gtc 399 Ala Pro Ser Lys Val Lys Leu Val Phe Ile Arg AsnGlu Asp Ala Val 95 100 105 aat cag atg gcc gtt act ccc ttt cca gtg ccatca agt tct cca tct 447 Asn Gln Met Ala Val Thr Pro Phe Pro Val Pro SerSer Ser Pro Ser 110 115 120 125 tct att gag gat cag agc ggc acc gaa cctatt agt agt gag gaa gat 495 Ser Ile Glu Asp Gln Ser Gly Thr Glu Pro IleSer Ser Glu Glu Asp 130 135 140 ggc agc ctc gaa gtt ggt att aaa caa ttgcct gaa agt gaa agc ttc 543 Gly Ser Leu Glu Val Gly Ile Lys Gln Leu ProGlu Ser Glu Ser Phe 145 150 155 aaa ctg gct gtc agc cag atg aaa cag caaaaa tat cca aca aaa gtc 591 Lys Leu Ala Val Ser Gln Met Lys Gln Gln LysTyr Pro Thr Lys Val 160 165 170 tcc ttc agt tca caa gag ata cca tta gcacca gct tca tca tac cat 639 Ser Phe Ser Ser Gln Glu Ile Pro Leu Ala ProAla Ser Ser Tyr His 175 180 185 tca aca gat gca gac ttc aca ggc tat ggtggt ttc cag gct cct ctg 687 Ser Thr Asp Ala Asp Phe Thr Gly Tyr Gly GlyPhe Gln Ala Pro Leu 190 195 200 205 tca gtg gac ccc gca acg tgt ccc attgtc cct gga cag gaa atg att 735 Ser Val Asp Pro Ala Thr Cys Pro Ile ValPro Gly Gln Glu Met Ile 210 215 220 ata gaa ata tcc aag gga cgt tca gggctt ggt ctc agc att gtg gga 783 Ile Glu Ile Ser Lys Gly Arg Ser Gly LeuGly Leu Ser Ile Val Gly 225 230 235 gga aaa gac aca ccc ttg ttc tgg aggctg gga agt cca aga gca tgg 831 Gly Lys Asp Thr Pro Leu Phe Trp Arg LeuGly Ser Pro Arg Ala Trp 240 245 250 agc cag cat ctg gtg agg gcc ttc atgctg cat cat cct gtg aca gaa 879 Ser Gln His Leu Val Arg Ala Phe Met LeuHis His Pro Val Thr Glu 255 260 265 gtt gaa ggg caa aat gct ata gtt atccat gaa gtc tat gaa gaa ggg 927 Val Glu Gly Gln Asn Ala Ile Val Ile HisGlu Val Tyr Glu Glu Gly 270 275 280 285 gca gca gcc aga gat gga aga ctttgg gct ggt gac cag ata tta gag 975 Ala Ala Ala Arg Asp Gly Arg Leu TrpAla Gly Asp Gln Ile Leu Glu 290 295 300 gtt aat ggg gtt gac ctg agg aactcc agc cac gaa gaa gcc atc aca 1023 Val Asn Gly Val Asp Leu Arg Asn SerSer His Glu Glu Ala Ile Thr 305 310 315 gcc ctg agg cag acc ccc cag aaggtg cgg ctg gtg gtg tat aga gat 1071 Ala Leu Arg Gln Thr Pro Gln Lys ValArg Leu Val Val Tyr Arg Asp 320 325 330 gag gca cac tac cgg gat gag gagaac ttg gag att ttc cct gtg gat 1119 Glu Ala His Tyr Arg Asp Glu Glu AsnLeu Glu Ile Phe Pro Val Asp 335 340 345 ctg cag aag aaa gct ggc cgg ggcctg ggc ctg agc atc gtt ggg aaa 1167 Leu Gln Lys Lys Ala Gly Arg Gly LeuGly Leu Ser Ile Val Gly Lys 350 355 360 365 cgg aat gga agc gga gtg tttatt tct gac atc gtg aaa ggc gga gcc 1215 Arg Asn Gly Ser Gly Val Phe IleSer Asp Ile Val Lys Gly Gly Ala 370 375 380 gca gac ctg gat ggg aga ttgatt cag gga gat cag atc tta tct gtg 1263 Ala Asp Leu Asp Gly Arg Leu IleGln Gly Asp Gln Ile Leu Ser Val 385 390 395 aat ggg gag gac atg aga aatgcc tca cag gag aca gtg gcc acc atc 1311 Asn Gly Glu Asp Met Arg Asn AlaSer Gln Glu Thr Val Ala Thr Ile 400 405 410 ctc aag tgt gca cag gga cttgtg cag cta gag att gga aga ctc cga 1359 Leu Lys Cys Ala Gln Gly Leu ValGln Leu Glu Ile Gly Arg Leu Arg 415 420 425 gct ggt tcc tgg acc tcc gcaagg acg aca tca cag aac agt cag ggt 1407 Ala Gly Ser Trp Thr Ser Ala ArgThr Thr Ser Gln Asn Ser Gln Gly 430 435 440 445 agt cag cag agt gca cacagc agc tgt cat ccc tcc ttc gct cct gtc 1455 Ser Gln Gln Ser Ala His SerSer Cys His Pro Ser Phe Ala Pro Val 450 455 460 atc act ggc ctg caa aacctg gtt ggc aca aaa aga gtt tca gat cct 1503 Ile Thr Gly Leu Gln Asn LeuVal Gly Thr Lys Arg Val Ser Asp Pro 465 470 475 tcc cag aaa aca gat atggaa cca agg act gtt gag ata aac agg gag 1551 Ser Gln Lys Thr Asp Met GluPro Arg Thr Val Glu Ile Asn Arg Glu 480 485 490 ctc agt gat gcc ctt ggaatc agt att gct gga gga aga gga agt ccc 1599 Leu Ser Asp Ala Leu Gly IleSer Ile Ala Gly Gly Arg Gly Ser Pro 495 500 505 tta gga gat atc ccc gtattt att gcc atg att cag gct agc gga gtg 1647 Leu Gly Asp Ile Pro Val PheIle Ala Met Ile Gln Ala Ser Gly Val 510 515 520 525 gcc gca cgg aca cagaag ctt aaa gta gga gat cgg att gtc agc att 1695 Ala Ala Arg Thr Gln LysLeu Lys Val Gly Asp Arg Ile Val Ser Ile 530 535 540 aac ggg caa cct ttggat ggg ctg tct cac gcg gat gtg gtt aat ctg 1743 Asn Gly Gln Pro Leu AspGly Leu Ser His Ala Asp Val Val Asn Leu 545 550 555 ctg aag aac gcc tacggg cgc att atc ctg cag gta gta gca gat acc 1791 Leu Lys Asn Ala Tyr GlyArg Ile Ile Leu Gln Val Val Ala Asp Thr 560 565 570 aat ata agc gcc atagca gct cag ctt gaa aac atg tct aca ggc tac 1839 Asn Ile Ser Ala Ile AlaAla Gln Leu Glu Asn Met Ser Thr Gly Tyr 575 580 585 cac ctt ggt tcg cccact gct gaa cac cat cca gaa gac aca gag 1884 His Leu Gly Ser Pro Thr AlaGlu His His Pro Glu Asp Thr Glu 590 595 600 tgagtatttc agatgcagag g 190580 604 PRT Homo sapiens 80 Met Val Gln Gly Gly Phe Pro Glu Lys Ile ArgGln Arg Tyr Ala Asp 1 5 10 15 Leu Pro Gly Glu Leu His Ile Ile Glu LeuGlu Lys Asp Lys Asn Gly 20 25 30 Leu Gly Leu Ser Leu Ala Gly Asn Lys AspArg Ser Arg Met Ser Ile 35 40 45 Phe Val Val Gly Ile Asn Pro Glu Gly ProAla Ala Ala Asp Gly Arg 50 55 60 Met His Ile Gly Asp Glu Leu Leu Glu IleAsn Asn Gln Ile Leu Tyr 65 70 75 80 Gly Arg Ser His Gln Asn Ala Ser AlaIle Ile Lys Thr Ala Pro Ser 85 90 95 Lys Val Lys Leu Val Phe Ile Arg AsnGlu Asp Ala Val Asn Gln Met 100 105 110 Ala Val Thr Pro Phe Pro Val ProSer Ser Ser Pro Ser Ser Ile Glu 115 120 125 Asp Gln Ser Gly Thr Glu ProIle Ser Ser Glu Glu Asp Gly Ser Leu 130 135 140 Glu Val Gly Ile Lys GlnLeu Pro Glu Ser Glu Ser Phe Lys Leu Ala 145 150 155 160 Val Ser Gln MetLys Gln Gln Lys Tyr Pro Thr Lys Val Ser Phe Ser 165 170 175 Ser Gln GluIle Pro Leu Ala Pro Ala Ser Ser Tyr His Ser Thr Asp 180 185 190 Ala AspPhe Thr Gly Tyr Gly Gly Phe Gln Ala Pro Leu Ser Val Asp 195 200 205 ProAla Thr Cys Pro Ile Val Pro Gly Gln Glu Met Ile Ile Glu Ile 210 215 220Ser Lys Gly Arg Ser Gly Leu Gly Leu Ser Ile Val Gly Gly Lys Asp 225 230235 240 Thr Pro Leu Phe Trp Arg Leu Gly Ser Pro Arg Ala Trp Ser Gln His245 250 255 Leu Val Arg Ala Phe Met Leu His His Pro Val Thr Glu Val GluGly 260 265 270 Gln Asn Ala Ile Val Ile His Glu Val Tyr Glu Glu Gly AlaAla Ala 275 280 285 Arg Asp Gly Arg Leu Trp Ala Gly Asp Gln Ile Leu GluVal Asn Gly 290 295 300 Val Asp Leu Arg Asn Ser Ser His Glu Glu Ala IleThr Ala Leu Arg 305 310 315 320 Gln Thr Pro Gln Lys Val Arg Leu Val ValTyr Arg Asp Glu Ala His 325 330 335 Tyr Arg Asp Glu Glu Asn Leu Glu IlePhe Pro Val Asp Leu Gln Lys 340 345 350 Lys Ala Gly Arg Gly Leu Gly LeuSer Ile Val Gly Lys Arg Asn Gly 355 360 365 Ser Gly Val Phe Ile Ser AspIle Val Lys Gly Gly Ala Ala Asp Leu 370 375 380 Asp Gly Arg Leu Ile GlnGly Asp Gln Ile Leu Ser Val Asn Gly Glu 385 390 395 400 Asp Met Arg AsnAla Ser Gln Glu Thr Val Ala Thr Ile Leu Lys Cys 405 410 415 Ala Gln GlyLeu Val Gln Leu Glu Ile Gly Arg Leu Arg Ala Gly Ser 420 425 430 Trp ThrSer Ala Arg Thr Thr Ser Gln Asn Ser Gln Gly Ser Gln Gln 435 440 445 SerAla His Ser Ser Cys His Pro Ser Phe Ala Pro Val Ile Thr Gly 450 455 460Leu Gln Asn Leu Val Gly Thr Lys Arg Val Ser Asp Pro Ser Gln Lys 465 470475 480 Thr Asp Met Glu Pro Arg Thr Val Glu Ile Asn Arg Glu Leu Ser Asp485 490 495 Ala Leu Gly Ile Ser Ile Ala Gly Gly Arg Gly Ser Pro Leu GlyAsp 500 505 510 Ile Pro Val Phe Ile Ala Met Ile Gln Ala Ser Gly Val AlaAla Arg 515 520 525 Thr Gln Lys Leu Lys Val Gly Asp Arg Ile Val Ser IleAsn Gly Gln 530 535 540 Pro Leu Asp Gly Leu Ser His Ala Asp Val Val AsnLeu Leu Lys Asn 545 550 555 560 Ala Tyr Gly Arg Ile Ile Leu Gln Val ValAla Asp Thr Asn Ile Ser 565 570 575 Ala Ile Ala Ala Gln Leu Glu Asn MetSer Thr Gly Tyr His Leu Gly 580 585 590 Ser Pro Thr Ala Glu His His ProGlu Asp Thr Glu 595 600 81 1563 DNA Homo sapiens CDS (88)..(1179) 81accagttttt ccccagcacc accatcaagg cctcgaggct cccagctccc tctacagcct 60gtggactgac ttagggaatc ccgaacg atg aca gaa aag gag gtg ctg gag tcc 114Met Thr Glu Lys Glu Val Leu Glu Ser 1 5 cct aag ccc tcc ttc cca gca gagact cgg caa agt ggg cta cag cgg 162 Pro Lys Pro Ser Phe Pro Ala Glu ThrArg Gln Ser Gly Leu Gln Arg 10 15 20 25 cta aag cag tta ctc agg aag ggttct aca ggg aca aag gag atg gaa 210 Leu Lys Gln Leu Leu Arg Lys Gly SerThr Gly Thr Lys Glu Met Glu 30 35 40 ctt ccc cca gag ccc cag gcc aat ggggag gca gtg gga gct ggg ggt 258 Leu Pro Pro Glu Pro Gln Ala Asn Gly GluAla Val Gly Ala Gly Gly 45 50 55 ggg ccc atc tac tac atc tat gag gaa gaggaa gag gaa gaa gag gag 306 Gly Pro Ile Tyr Tyr Ile Tyr Glu Glu Glu GluGlu Glu Glu Glu Glu 60 65 70 gag gag gag cca ccc cca gaa cct cct aag ctggtc aac gat aag ccc 354 Glu Glu Glu Pro Pro Pro Glu Pro Pro Lys Leu ValAsn Asp Lys Pro 75 80 85 cac aaa ttc aaa gat cac ttc ttc aag aag cca aagttc tgt gat gtc 402 His Lys Phe Lys Asp His Phe Phe Lys Lys Pro Lys PheCys Asp Val 90 95 100 105 tgt gcc cgg atg att gtt ctc aac aac aag tttggg ctt cgc tgt aag 450 Cys Ala Arg Met Ile Val Leu Asn Asn Lys Phe GlyLeu Arg Cys Lys 110 115 120 aac tgc aaa acc aac atc cat gaa cac tgt cagtcc tat gtg gaa atg 498 Asn Cys Lys Thr Asn Ile His Glu His Cys Gln SerTyr Val Glu Met 125 130 135 cag aga tgc ttc ggc aag atc cca cct ggt ttccat cgg gcc tat agt 546 Gln Arg Cys Phe Gly Lys Ile Pro Pro Gly Phe HisArg Ala Tyr Ser 140 145 150 tcc cca ctc tac agc aac cag cag tac gct tgtgtc aaa gat ctc tct 594 Ser Pro Leu Tyr Ser Asn Gln Gln Tyr Ala Cys ValLys Asp Leu Ser 155 160 165 gct gcc aat cgc aat gat cct gtg ttt gaa accctg cgc act ggg gtg 642 Ala Ala Asn Arg Asn Asp Pro Val Phe Glu Thr LeuArg Thr Gly Val 170 175 180 185 atc atg gca aac aag gaa cgg aag aag ggacag gca gat aag aaa aat 690 Ile Met Ala Asn Lys Glu Arg Lys Lys Gly GlnAla Asp Lys Lys Asn 190 195 200 cct gta gca gcc atg atg gag gag gag ccagag tcg gcc aga cca gag 738 Pro Val Ala Ala Met Met Glu Glu Glu Pro GluSer Ala Arg Pro Glu 205 210 215 gaa ggc aaa ccc cag gat gga aac cct gaaggg gat aag aag gct gag 786 Glu Gly Lys Pro Gln Asp Gly Asn Pro Glu GlyAsp Lys Lys Ala Glu 220 225 230 aag aag aca cct gat gac aag cac aag cagcct ggc ttc cag cag tct 834 Lys Lys Thr Pro Asp Asp Lys His Lys Gln ProGly Phe Gln Gln Ser 235 240 245 cat tac ttt gtg gct ctc tat cgg ttc aaagcc ctg gag aag gac gat 882 His Tyr Phe Val Ala Leu Tyr Arg Phe Lys AlaLeu Glu Lys Asp Asp 250 255 260 265 ctg gat ttc ccg cca gga gag aag atcaca gtc att gat gac tcc aat 930 Leu Asp Phe Pro Pro Gly Glu Lys Ile ThrVal Ile Asp Asp Ser Asn 270 275 280 gaa gaa tgg tgg cgg ggg aaa atc ggggag aag gtc gga ttt ttc cct 978 Glu Glu Trp Trp Arg Gly Lys Ile Gly GluLys Val Gly Phe Phe Pro 285 290 295 cca aac ttc atc att cgg gtc cgg gctgga gaa cgt gtg cac cgc gtg 1026 Pro Asn Phe Ile Ile Arg Val Arg Ala GlyGlu Arg Val His Arg Val 300 305 310 acg aga tcc ttc gtg ggg aac cgc gagata ggg cag atc act ctc aag 1074 Thr Arg Ser Phe Val Gly Asn Arg Glu IleGly Gln Ile Thr Leu Lys 315 320 325 aag gac cag atc gtg gtg cag aaa ggagac gaa gcg ggc ggc tac gtc 1122 Lys Asp Gln Ile Val Val Gln Lys Gly AspGlu Ala Gly Gly Tyr Val 330 335 340 345 aag gtc tac acc ggc cgc aag gtgggg ctg ttt ccc acc gac ttt cta 1170 Lys Val Tyr Thr Gly Arg Lys Val GlyLeu Phe Pro Thr Asp Phe Leu 350 355 360 gag gaa att taggcgtgcgggcgcctgca agcgggagac acccacaccc 1219 Glu Glu Ile cattctgggc gggcccagtggagtttgggg aggggggcga aagcaacggg actgctggga 1279 gaggaggggt aggaaggcccgcctgagcgc gacggggctt ccgggaaggg actggttctc 1339 gcccccttcc ccagcctggggcctcggata cctgctgccc agagcagccc ggacccgaaa 1399 cctttcaggc cccgcttgcaagagctggaa aaaaacgcgt atctactagg aggagccagg 1459 gactggggcg gggggcgggggcgagggagg gcgaactgtc gaatgttgcg aatttattaa 1519 acttttgaca aaacttaaaaaaaaaaaaaa aaaaaaaaaa aaaa 1563 82 364 PRT Homo sapiens 82 Met Thr GluLys Glu Val Leu Glu Ser Pro Lys Pro Ser Phe Pro Ala 1 5 10 15 Glu ThrArg Gln Ser Gly Leu Gln Arg Leu Lys Gln Leu Leu Arg Lys 20 25 30 Gly SerThr Gly Thr Lys Glu Met Glu Leu Pro Pro Glu Pro Gln Ala 35 40 45 Asn GlyGlu Ala Val Gly Ala Gly Gly Gly Pro Ile Tyr Tyr Ile Tyr 50 55 60 Glu GluGlu Glu Glu Glu Glu Glu Glu Glu Glu Glu Pro Pro Pro Glu 65 70 75 80 ProPro Lys Leu Val Asn Asp Lys Pro His Lys Phe Lys Asp His Phe 85 90 95 PheLys Lys Pro Lys Phe Cys Asp Val Cys Ala Arg Met Ile Val Leu 100 105 110Asn Asn Lys Phe Gly Leu Arg Cys Lys Asn Cys Lys Thr Asn Ile His 115 120125 Glu His Cys Gln Ser Tyr Val Glu Met Gln Arg Cys Phe Gly Lys Ile 130135 140 Pro Pro Gly Phe His Arg Ala Tyr Ser Ser Pro Leu Tyr Ser Asn Gln145 150 155 160 Gln Tyr Ala Cys Val Lys Asp Leu Ser Ala Ala Asn Arg AsnAsp Pro 165 170 175 Val Phe Glu Thr Leu Arg Thr Gly Val Ile Met Ala AsnLys Glu Arg 180 185 190 Lys Lys Gly Gln Ala Asp Lys Lys Asn Pro Val AlaAla Met Met Glu 195 200 205 Glu Glu Pro Glu Ser Ala Arg Pro Glu Glu GlyLys Pro Gln Asp Gly 210 215 220 Asn Pro Glu Gly Asp Lys Lys Ala Glu LysLys Thr Pro Asp Asp Lys 225 230 235 240 His Lys Gln Pro Gly Phe Gln GlnSer His Tyr Phe Val Ala Leu Tyr 245 250 255 Arg Phe Lys Ala Leu Glu LysAsp Asp Leu Asp Phe Pro Pro Gly Glu 260 265 270 Lys Ile Thr Val Ile AspAsp Ser Asn Glu Glu Trp Trp Arg Gly Lys 275 280 285 Ile Gly Glu Lys ValGly Phe Phe Pro Pro Asn Phe Ile Ile Arg Val 290 295 300 Arg Ala Gly GluArg Val His Arg Val Thr Arg Ser Phe Val Gly Asn 305 310 315 320 Arg GluIle Gly Gln Ile Thr Leu Lys Lys Asp Gln Ile Val Val Gln 325 330 335 LysGly Asp Glu Ala Gly Gly Tyr Val Lys Val Tyr Thr Gly Arg Lys 340 345 350Val Gly Leu Phe Pro Thr Asp Phe Leu Glu Glu Ile 355 360 83 1563 DNA Homosapiens CDS (88)..(1179) 83 accagttttt ccccagcacc accatcaagg cctcgaggctcccagctccc tctacagcct 60 gtggactgac ttagggaatc ccgaacg atg aca gaa aaggag gtg ctg gag tcc 114 Met Thr Glu Lys Glu Val Leu Glu Ser 1 5 cct aagccc tcc ttc cca gca gag act cgg caa agt ggg cta cag cgg 162 Pro Lys ProSer Phe Pro Ala Glu Thr Arg Gln Ser Gly Leu Gln Arg 10 15 20 25 cta aagcag tta ctc agg aag ggt tct aca ggg aca aag gag atg gaa 210 Leu Lys GlnLeu Leu Arg Lys Gly Ser Thr Gly Thr Lys Glu Met Glu 30 35 40 ctt ccc ccagag ccc cag gcc aat ggg gag gca gtg gga gct ggg ggt 258 Leu Pro Pro GluPro Gln Ala Asn Gly Glu Ala Val Gly Ala Gly Gly 45 50 55 ggg ccc atc tactac atc tat gag gaa gag gaa gag gaa gaa gag gag 306 Gly Pro Ile Tyr TyrIle Tyr Glu Glu Glu Glu Glu Glu Glu Glu Glu 60 65 70 gag gag gag cca ccccca gaa cct cct aag ctg gtc aac gat aag ccc 354 Glu Glu Glu Pro Pro ProGlu Pro Pro Lys Leu Val Asn Asp Lys Pro 75 80 85 cac aaa ttc aaa gat cacttc ttc aag aag cca aag ttc tgt gat gtc 402 His Lys Phe Lys Asp His PhePhe Lys Lys Pro Lys Phe Cys Asp Val 90 95 100 105 tgt gcc cgg atg attgtt ctc aac aac aag ttt ggg ctt cgc tgt aag 450 Cys Ala Arg Met Ile ValLeu Asn Asn Lys Phe Gly Leu Arg Cys Lys 110 115 120 aac tgc aaa acc aacatc cat gaa cac tgt cag tcc tat gtg gaa atg 498 Asn Cys Lys Thr Asn IleHis Glu His Cys Gln Ser Tyr Val Glu Met 125 130 135 cag aga tgc ttc ggcaag atc cca cct ggt ttc cat cgg gcc tat agt 546 Gln Arg Cys Phe Gly LysIle Pro Pro Gly Phe His Arg Ala Tyr Ser 140 145 150 tcc cca ctc tac agcaac cag cag tac gct tgt gtc aaa gat ctc tct 594 Ser Pro Leu Tyr Ser AsnGln Gln Tyr Ala Cys Val Lys Asp Leu Ser 155 160 165 gct gcc aat cgc aatgat cct gtg ttt gaa acc ctg cgc act ggg gtg 642 Ala Ala Asn Arg Asn AspPro Val Phe Glu Thr Leu Arg Thr Gly Val 170 175 180 185 atc atg gca aacaag gaa cgg aag aag gga cag gca gat aag aaa aat 690 Ile Met Ala Asn LysGlu Arg Lys Lys Gly Gln Ala Asp Lys Lys Asn 190 195 200 cct gta gca gccatg atg gag gag gag cca gag tcg gcc aga cca gag 738 Pro Val Ala Ala MetMet Glu Glu Glu Pro Glu Ser Ala Arg Pro Glu 205 210 215 gaa ggc aaa ccccag gat gga aac cct gaa ggg gat aag aag gct gag 786 Glu Gly Lys Pro GlnAsp Gly Asn Pro Glu Gly Asp Lys Lys Ala Glu 220 225 230 aag aag aca cctgat gac aag cac aag cag cct ggc ttc cag cag tct 834 Lys Lys Thr Pro AspAsp Lys His Lys Gln Pro Gly Phe Gln Gln Ser 235 240 245 cat tac ttt gtggct ctc tat cgg ttc aaa gcc ctg gag aag gac gat 882 His Tyr Phe Val AlaLeu Tyr Arg Phe Lys Ala Leu Glu Lys Asp Asp 250 255 260 265 ctg gat ttcccg cca gga gag aag atc aca gtc att gat gac tcc aat 930 Leu Asp Phe ProPro Gly Glu Lys Ile Thr Val Ile Asp Asp Ser Asn 270 275 280 gaa gaa tggtgg cgg ggg aaa atc ggg gag aag gtc gga ttt ttc cct 978 Glu Glu Trp TrpArg Gly Lys Ile Gly Glu Lys Val Gly Phe Phe Pro 285 290 295 cca aac ttcatc att cgg gtc cgg gct gga gaa cgt gtg cac cgc gtg 1026 Pro Asn Phe IleIle Arg Val Arg Ala Gly Glu Arg Val His Arg Val 300 305 310 acg aga tccttc gtg ggg aac cgc gag ata ggg cag atc act ctc aag 1074 Thr Arg Ser PheVal Gly Asn Arg Glu Ile Gly Gln Ile Thr Leu Lys 315 320 325 aag gac cagatc gtg gtg cag aaa gga gac gaa gcg ggc ggc tac gtc 1122 Lys Asp Gln IleVal Val Gln Lys Gly Asp Glu Ala Gly Gly Tyr Val 330 335 340 345 aag gtctac acc ggc cgc aag gtg ggg ctg ttt ccc acc gac ttt cta 1170 Lys Val TyrThr Gly Arg Lys Val Gly Leu Phe Pro Thr Asp Phe Leu 350 355 360 gag gaaatt taggcgtgcg ggcgcctgca agcgggagac acccacaccc 1219 Glu Glu Ilecattctgggc gggcccagtg gagtttgggg aggggggcga aagcaacggg actgctggga 1279gaggaggggt aggaaggccc gcctgagcgc gacggggctt ccgggaaggg actggttctc 1339gcccccttcc ccagcctggg gcctcggata cctgctgccc agagcagccc ggacccgaaa 1399cctttcaggc cccgcttgca agagctggaa aaaaacgcgt atctactagg aggagccagg 1459gactggggcg gggggcgggg gcgagggagg gcgaactgtc gaatgttgcg aatttattaa 1519acttttgaca aaacttaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1563 84 364 PRT Homosapiens 84 Met Thr Glu Lys Glu Val Leu Glu Ser Pro Lys Pro Ser Phe ProAla 1 5 10 15 Glu Thr Arg Gln Ser Gly Leu Gln Arg Leu Lys Gln Leu LeuArg Lys 20 25 30 Gly Ser Thr Gly Thr Lys Glu Met Glu Leu Pro Pro Glu ProGln Ala 35 40 45 Asn Gly Glu Ala Val Gly Ala Gly Gly Gly Pro Ile Tyr TyrIle Tyr 50 55 60 Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Pro ProPro Glu 65 70 75 80 Pro Pro Lys Leu Val Asn Asp Lys Pro His Lys Phe LysAsp His Phe 85 90 95 Phe Lys Lys Pro Lys Phe Cys Asp Val Cys Ala Arg MetIle Val Leu 100 105 110 Asn Asn Lys Phe Gly Leu Arg Cys Lys Asn Cys LysThr Asn Ile His 115 120 125 Glu His Cys Gln Ser Tyr Val Glu Met Gln ArgCys Phe Gly Lys Ile 130 135 140 Pro Pro Gly Phe His Arg Ala Tyr Ser SerPro Leu Tyr Ser Asn Gln 145 150 155 160 Gln Tyr Ala Cys Val Lys Asp LeuSer Ala Ala Asn Arg Asn Asp Pro 165 170 175 Val Phe Glu Thr Leu Arg ThrGly Val Ile Met Ala Asn Lys Glu Arg 180 185 190 Lys Lys Gly Gln Ala AspLys Lys Asn Pro Val Ala Ala Met Met Glu 195 200 205 Glu Glu Pro Glu SerAla Arg Pro Glu Glu Gly Lys Pro Gln Asp Gly 210 215 220 Asn Pro Glu GlyAsp Lys Lys Ala Glu Lys Lys Thr Pro Asp Asp Lys 225 230 235 240 His LysGln Pro Gly Phe Gln Gln Ser His Tyr Phe Val Ala Leu Tyr 245 250 255 ArgPhe Lys Ala Leu Glu Lys Asp Asp Leu Asp Phe Pro Pro Gly Glu 260 265 270Lys Ile Thr Val Ile Asp Asp Ser Asn Glu Glu Trp Trp Arg Gly Lys 275 280285 Ile Gly Glu Lys Val Gly Phe Phe Pro Pro Asn Phe Ile Ile Arg Val 290295 300 Arg Ala Gly Glu Arg Val His Arg Val Thr Arg Ser Phe Val Gly Asn305 310 315 320 Arg Glu Ile Gly Gln Ile Thr Leu Lys Lys Asp Gln Ile ValVal Gln 325 330 335 Lys Gly Asp Glu Ala Gly Gly Tyr Val Lys Val Tyr ThrGly Arg Lys 340 345 350 Val Gly Leu Phe Pro Thr Asp Phe Leu Glu Glu Ile355 360 85 1912 DNA Homo sapiens CDS (184)..(513) 85 ccggcggctgttgtcgggcc tccagcgggc ggggccgttg gcggagcaga gcggaggcgc 60 agccgggcggagggcccacg agggctcagc cttcccggtc agcggtggtg acggtatccc 120 agagtgccagagaaccgttg cttttccgag ttgctcttct tccaggctcc gttggtggtc 180 ggc atg gcccgt gga aat caa cga gaa ctt gcc cgc cag aaa aac atg 228 Met Ala Arg GlyAsn Gln Arg Glu Leu Ala Arg Gln Lys Asn Met 1 5 10 15 aag aaa acc caggaa att agc aag gga aag agg aaa gag gat agc ttg 276 Lys Lys Thr Gln GluIle Ser Lys Gly Lys Arg Lys Glu Asp Ser Leu 20 25 30 act gcc tct cag agaaag cag agt tct gga ggc cag aaa tct gag agc 324 Thr Ala Ser Gln Arg LysGln Ser Ser Gly Gly Gln Lys Ser Glu Ser 35 40 45 aag atg tca gct ggg ccacac ctc cct ctg aag gct cca agg gag aat 372 Lys Met Ser Ala Gly Pro HisLeu Pro Leu Lys Ala Pro Arg Glu Asn 50 55 60 cct tgc ttt cct ctt cca gctgct ggt ggc tcc agg tat tac ttg gct 420 Pro Cys Phe Pro Leu Pro Ala AlaGly Gly Ser Arg Tyr Tyr Leu Ala 65 70 75 tat ggc agc ata act cct atc tctgcc ttt gtc ttt gtg gtc ttc ttt 468 Tyr Gly Ser Ile Thr Pro Ile Ser AlaPhe Val Phe Val Val Phe Phe 80 85 90 95 tct gtc ttc ttc cct tct ttt tatgag gac ttt tgc tgt tgg att 513 Ser Val Phe Phe Pro Ser Phe Tyr Glu AspPhe Cys Cys Trp Ile 100 105 110 taggttccat tctaacctag gatgatctcatttggaaatc cttaatttca tctacaaaaa 573 ctgttttccc aaataggtca cattcacgcatatcagatgg acagatgtat cattttgggg 633 tccaccattc aacccactac aaggagttttttaaacaaaa ataggaaact tagatgtaac 693 ttagcacttt tttttttttt ttttgagatggagtctcact ctgtcaccag actggagtgc 753 agtggcgcca tctcagctcc atgcaacctctgcctcctgg gttcaagcag ttctcttgcc 813 tcagcctcct gggtagctgg gattacaggcacgcgctgcc acacccaggt aatttattta 873 tttttttttt gagacagagt ctcgcactgttgcccaggct ggactgcagt ggcgtgatct 933 ctgctcactg caacctccgc ctcccgggttcaagcgattc tccagcctca gcttcctgag 993 tagatgggat tacaggcgcc tgccaccacgcccagctaat ttttttgtat tcttagtaga 1053 gatggggttt caccatgttg gccaggctggtctccatctc ctgacctcgt gattcacccg 1113 cctcggcctc ccaaagtgct gggattacaggcgtgagtca cagcccccgg ccataattta 1173 gcactttaaa aaataatagc catgttgggccaggcgtggt ggctcatgcc tgtaatctga 1233 gcactttggg agaccaaggc gggtagatcccttgtgccca ggagttcaag accagcctgg 1293 gcaacatggc gaaaccccat ttctactaaaaatacaaaaa ttagctgggg cgaggggata 1353 ggccgagttc cgggtgtaag ggggccattagggagagcag agcgaggcag ctgatcttcc 1413 ggattggggg ccttgcccgg aagctggacctcacggagat gaaacggaag atgcacgagg 1473 atatgatctc catacagaac tttctcatctacgtggccct gctgcgagtc actccattta 1533 tcttaaagaa attggacagc atatgaagattggacatcac atgtgaatgc atgatatgaa 1593 gagcctggtt acagtttcta ctgttctctgcaagtaaata ggcccagaaa ggtataagag 1653 actctttgaa tggacataaa aattctgcttgttaagaaca agttgagctc tggtaactga 1713 tcttaatagc taaaatataa aaatatttgggaagtctgaa atgaggtctc ctggccctgg 1773 tgtgccctta atgcctgtga cagttggcctctgtgaatat tggtataatt gtaaataatg 1833 tcaaactcca ttttctagca agtattaataattaagggaa gtatgtctga aatggcaaaa 1893 aaaaaaaaaa aaaaaaaaa 1912 86 110PRT Homo sapiens 86 Met Ala Arg Gly Asn Gln Arg Glu Leu Ala Arg Gln LysAsn Met Lys 1 5 10 15 Lys Thr Gln Glu Ile Ser Lys Gly Lys Arg Lys GluAsp Ser Leu Thr 20 25 30 Ala Ser Gln Arg Lys Gln Ser Ser Gly Gly Gln LysSer Glu Ser Lys 35 40 45 Met Ser Ala Gly Pro His Leu Pro Leu Lys Ala ProArg Glu Asn Pro 50 55 60 Cys Phe Pro Leu Pro Ala Ala Gly Gly Ser Arg TyrTyr Leu Ala Tyr 65 70 75 80 Gly Ser Ile Thr Pro Ile Ser Ala Phe Val PheVal Val Phe Phe Ser 85 90 95 Val Phe Phe Pro Ser Phe Tyr Glu Asp Phe CysCys Trp Ile 100 105 110 87 255 DNA Homo sapiens CDS (1)..(255) 87 ggatcc gcc cgt gga aat caa cga gaa ctt gtc cgc cag aaa aac atg 48 Gly SerAla Arg Gly Asn Gln Arg Glu Leu Val Arg Gln Lys Asn Met 1 5 10 15 aagaaa acc cag gaa att agc aag gga aag agg aaa gag gat agc ttg 96 Lys LysThr Gln Glu Ile Ser Lys Gly Lys Arg Lys Glu Asp Ser Leu 20 25 30 act gcctct cag aga aag cag agt tct gga ggc cag aaa tct gag agc 144 Thr Ala SerGln Arg Lys Gln Ser Ser Gly Gly Gln Lys Ser Glu Ser 35 40 45 aag atg tcagct ggg cca cac ctc cct ctg gag gct cca agg gag aat 192 Lys Met Ser AlaGly Pro His Leu Pro Leu Glu Ala Pro Arg Glu Asn 50 55 60 cct tgc ttt cctctt cca gct gct ggt ggc tac agg tat tac ttg gct 240 Pro Cys Phe Pro LeuPro Ala Ala Gly Gly Tyr Arg Tyr Tyr Leu Ala 65 70 75 80 tat ggc agc ctcgag 255 Tyr Gly Ser Leu Glu 85 88 85 PRT Homo sapiens 88 Gly Ser Ala ArgGly Asn Gln Arg Glu Leu Val Arg Gln Lys Asn Met 1 5 10 15 Lys Lys ThrGln Glu Ile Ser Lys Gly Lys Arg Lys Glu Asp Ser Leu 20 25 30 Thr Ala SerGln Arg Lys Gln Ser Ser Gly Gly Gln Lys Ser Glu Ser 35 40 45 Lys Met SerAla Gly Pro His Leu Pro Leu Glu Ala Pro Arg Glu Asn 50 55 60 Pro Cys PhePro Leu Pro Ala Ala Gly Gly Tyr Arg Tyr Tyr Leu Ala 65 70 75 80 Tyr GlySer Leu Glu 85 89 20 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 89 tgatggcaaa ggaactggat 20 90 24 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 90 ccataccccattgaaatcgt gcca 24 91 20 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 91 aatcttgggg tcacaggctt 20 92 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 92ggtttgacag atctggaatg tg 22 93 26 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 93 ctattcctcc gcagtctggc ctgtct 26 94 21DNA Artificial Sequence Description of Artifical Sequence Primer/Probe94 gctggcaaag aagacagaaa g 21 95 22 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 95 gggttgagga agactaggag aa 22 96 26DNA Artificial Sequence Description of Artifical Sequence Primer/Probe96 actcaatgct atccaccatt acccag 26 97 22 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 97 ctgagggatt ttcttcttttcc 22 98 22 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 98 aacgggcaca ttaactttaa gc 22 99 26 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 99 ttctgggagatctccagaca gatcca 26 100 22 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 100 ctgtgtccat gtcatgaact ca 22 101 16DNA Artificial Sequence Description of Artifical Sequence Primer/Probe101 tgccgggtgg tgaaga 16 102 21 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 102 actccaacat gcgggcccgg t 21 103 16DNA Artificial Sequence Description of Artifical Sequence Primer/Probe103 actcccgggc cacatc 16 104 21 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 104 aggtagagtg ggatgccttc t 21 105 29DNA Artificial Sequence Description of Artifical Sequence Primer/Probe105 ccatccctga acttcagaac ttcctaaca 29 106 22 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 106 gattttgtcc tgctcctctttt 22 107 22 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 107 gctcttccag aaactctcca tt 22 108 23 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 108 ctctacctgcgcctgcttgc tgg 23 109 22 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 109 tcattctcct ttagcacaaa gc 22 110 20DNA Artificial Sequence Description of Artifical Sequence Primer/Probe110 tccacgatgg agaaagatgt 20 111 27 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 111 tcctcttcat tctgaaagtt catcaaa 27112 20 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 112 ttttgcttct tggtgctttc 20 113 22 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 113 gacaggatag tccagtggattg 22 114 24 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 114 atgcacaagg acagcacaag ccat 24 115 22 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 115 gaagacctttcccttcttga tg 22 116 20 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 116 caagcctgtc ttgttgctgt 20 117 26 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 117 tggcgcaaagctcaagaagt ctgtaa 26 118 20 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 118 tttcctaagg tttggccaac 20 119 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 119acaaaccatg gaagacttca ag 22 120 30 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 120 ccagaagaat atcctttaac tccagaaaca30 121 22 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 121 cttcccattt gttttcgtaa ca 22 122 22 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 122 agcttaaagatgacaccttg ca 22 123 29 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 123 tgtcagattt aacatacatc gattcagca 29 124 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 124ttctagaatg ctgccagttg at 22 125 20 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 125 ctggagaacc caggtaatgg 20 126 25DNA Artificial Sequence Description of Artifical Sequence Primer/Probe126 ccttctacct gcagtctctc gccct 25 127 21 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 127 tcatgggtca ggatgttctct 21 128 22 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 128 ctgacatgaa ggaactcaac ct 22 129 26 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 129 caacattgaaaacatcccca aagaaa 26 130 22 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 130 ttgcattgac aaagtccagt aa 22 131 22DNA Artificial Sequence Description of Artifical Sequence Primer/Probe131 ctgcaagttg caccttctag aa 22 132 26 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 132 agctcctctc acccagcgtaatgatg 26 133 22 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 133 atatgggtca caacatgatg gt 22 134 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 134tttgactcca gtgcagaaga tc 22 135 26 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 135 tcccttacag ttggctgagc tcctaa 26136 22 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 136 agctgccaca tacctgtagt ca 22 137 19 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 137 catcgatggactggagaca 19 138 24 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 138 aaatgcctcc acgtcgtgac agag 24 139 15 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 139cccaacgggg tcaca 15 140 19 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 140 ttgggagaga ccgtgtcat 19 141 30 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 141cagaaaccac caagttttat atgacagaga 30 142 22 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 142 ccaagacctt ggtatgatagga 22 143 21 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 143 acagcatcac tgcaaaactt g 21 144 26 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 144 aaaagttgctcctcttcttc gtgaaa 26 145 21 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 145 gaatggggca aagtctacaa a 21 146 22DNA Artificial Sequence Description of Artifical Sequence Primer/Probe146 cgtctaagtt cctggcatac tg 22 147 28 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 147 tcaacaaata tcaagtactcttgtgcca 28 148 22 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 148 tgggtaaata atggatgttt cg 22 149 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 149atgccttgat ctaccactgc ta 22 150 29 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 150 tcttttgtta aatgtaccat ccttccaga29 151 21 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 151 cttgtcttct ggcgactttt c 21 152 21 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 152 aaatcctcaggccttcagag t 21 153 26 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 153 aatctgtgat agatcttcgc ccagaa 26 154 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 154agccactttc atgtaccaca tc 22 155 22 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 155 gccagttcta cctcaagttc ct 22 15624 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 156 ctaccaccat gtgtcccgcc gttt 24 157 22 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 157 catagtcagagtcgagcagg aa 22 158 22 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 158 ttctcttact cccagcagtg aa 22 159 26 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 159cccaggccaa agtgagctca ctaaca 26 160 22 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 160 tcagagaaga gtgcagcaagat 22 161 19 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 161 atgggacaag gtgtgctga 19 162 28 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 162 tgtggattct cacatacagccaatctca 28 163 27 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 163 tttgtgtaca atattcttag cctctca 27 164 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 164aaatgtggca gatttcagaa aa 22 165 26 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 165 atggcttttc ccagaaacaa cagcaa 26166 22 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 166 gtaagcacaa aatccccgat at 22 167 21 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 167 ttccagtgtttgagcgttat g 21 168 26 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 168 tgagcgcatc acaagccttt aaattg 26 169 22 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 169caagggaatt ttattggtct ca 22 170 22 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 170 tattgcttgg tatggtgctg tt 22 17126 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 171 tgggaacaga caaaatcact tcactg 26 172 22 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 172 ggctgaagtcctgttgtact tg 22 173 20 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 173 agcctttgga cgagctgtac 20 174 26 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 174 gagactctgatggccaagga gtccac 26 175 20 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 175 acagcacgtc agcaaatagc 20 176 20 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 176tcagatggga agtggaagct 20 177 27 DNA Artificial Sequence Description ofArtifical Sequence Primer/Probe 177 ccagaaactg tttccctaca gagagca 27 17819 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 178 aggttcagca ttgccatct 19 179 22 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 179 gctaactgca ctccgagactta 22 180 26 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 180 tcctctcttc aactggatca gaaaga 26 181 21 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 181 cggctctgagaatctctcct a 21 182 22 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 182 cctgaagcac ctacagatca ac 22 183 24 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 183actggcctga ccaacctgct ggat 24 184 22 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 184 gaggtcctcc agtaagctgt ct 22 18520 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 185 tgctacccac gttcgtactg 20 186 26 DNA Artificial SequenceDescription of Artifical Sequence Primer/Probe 186 ctccttcctg aacaagctctccgact 26 187 21 DNA Artificial Sequence Description of ArtificalSequence Primer/Probe 187 gcaggtctgc gtggtagtag t 21 188 23 DNAArtificial Sequence Description of Artifical Sequence Primer/Probe 188ctgatggagc accttgttcc cac 23 189 28 DNA Artificial Sequence Descriptionof Artifical Sequence Primer/Probe 189 ctacctgagg gtcttccagc tgtctttt 28190 23 DNA Artificial Sequence Description of Artifical SequencePrimer/Probe 190 atggaaggag acttctcggt gtg 23 191 24 DNA ArtificialSequence Description of Artifical Sequence Primer/Probe 191 catcacctttcacaagacca ccac 24

What is claimed is:
 1. An isolated polypeptide comprising the matureform of an amino acid sequenced selected from the group consisting ofSEQ ID NO:2n, wherein n is an integer between 1 and
 44. 2. An isolatedpolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:2n, wherein n is an integer between 1 and
 44. 3.An isolated polypeptide comprising an amino acid sequence which is atleast 95% identical to an amino acid sequence selected from the groupconsisting of SEQ ID NO:2n, wherein n is an integer between 1 and
 44. 4.An isolated polypeptide, wherein the polypeptide comprises an amino acidsequence comprising one or more conservative substitutions in the aminoacid sequence selected from the group consisting of SEQ ID NO:2n,wherein n is an integer between 1 and
 44. 5. The polypeptide of claim 1wherein said polypeptide is naturally occurring.
 6. A compositioncomprising the polypeptide of claim 1 and a carrier.
 7. A kitcomprising, in one or more containers, the composition of claim
 6. 8.The use of a therapeutic in the manufacture of a medicament for treatinga syndrome associated with a human disease, the disease selected from apathology associated with the polypeptide of claim 1, wherein thetherapeutic comprises the polypeptide of claim
 1. 9. A method fordetermining the presence or amount of the polypeptide of claim 1 in asample, the method comprising: (a) providing said sample; (b)introducing said sample to an antibody that binds immunospecifically tothe polypeptide; and (c) determining the presence or amount of antibodybound to said polypeptide, thereby determining the presence or amount ofpolypeptide in said sample.
 10. A method for determining the presence ofor predisposition to a disease associated with altered levels ofexpression of the polypeptide of claim 1 in a first mammalian subject,the method comprising: a) measuring the level of expression of thepolypeptide in a sample from the first mammalian subject; and b)comparing the expression of said polypeptide in the sample of step (a)to the expression of the polypeptide present in a control sample from asecond mammalian subject known not to have, or not to be predisposed to,said disease. wherein an alteration in the level of expression of thepolypeptide in the first subject as compared to the control sampleindicates the presence of or predisposition to said disease.
 11. Amethod of identifying an agent that binds to the polypeptide of claim 1,the method comprising: (a) introducing said polypeptide to said agent;and (b) determining whether said agent binds to said polypeptide. 12.The method of claim 11 wherein the agent is a cellular receptor or adownstream effector.
 13. A method for identifying a potentialtherapeutic agent for use in treatment of a pathology, wherein thepathology is related to aberrant expression or aberrant physiologicalinteractions of the polypeptide of claim 1, the method comprising: (a)providing a cell expressing the polypeptide of claim 1 and having aproperty or function ascribable to the polypeptide; (b) contacting thecell with a composition comprising a candidate substance; and (c)determining whether the substance alters the property or functionascribable to the polypeptide; whereby, if an alteration observed in thepresence of the substance is not observed when the cell is contactedwith a composition in the absence of the substance, the substance isidentified as a potential therapeutic agent.
 14. A method for screeningfor a modulator of activity of or of latency or predisposition to apathology associated with the polypeptide of claim 1, said methodcomprising: (a) administering a test compound to a test animal atincreased risk for a pathology associated with the polypeptide of claim1, wherein said test animal recombinantly expresses the polypeptide ofclaim 1; (b) measuring the activity of said polypeptide in said testanimal after administering the compound of step (a); and (c) comparingthe activity of said polypeptide in said test animal with the activityof said polypeptide in a control animal not administered saidpolypeptide, wherein a change in the activity of said polypeptide insaid test animal relative to said control animal indicates the testcompound is a modulator activity of or latency or predisposition to, apathology associated with the polypeptide of claim
 1. 15. The method ofclaim 14, wherein said test animal is a recombinant test animal thatexpresses a test protein transgene or expresses said transgene under thecontrol of a promoter at an increased level relative to a wild-type testanimal, and wherein said promoter is not the native gene promoter ofsaid transgene.
 16. A method for modulating the activity of thepolypeptide of claim 1, the method comprising contacting a cell sampleexpressing the polypeptide of claim 1 with a compound that binds to saidpolypeptide in an amount sufficient to modulate the activity of thepolypeptide.
 17. A method of treating or preventing a pathologyassociated with the polypeptide of claim 1, the method comprisingadministering the polypeptide of claim 1 to a subject in which suchtreatment or prevention is desired in an amount sufficient to treat orprevent the pathology in the subject.
 18. The method of claim 17,wherein the subject is a human.
 19. A method of treating a pathologicalstate in a mammal, the method comprising administering to the mammal apolypeptide in an amount that is sufficient to alleviate thepathological state, wherein the polypeptide is a polypeptide having anamino acid sequence at least 95% identical to a polypeptide comprisingthe amino acid sequence selected from the group consisting of SEQ IDNO:2n, wherein n is an integer between 1 and 44 or a biologically activefragment thereof.
 20. An isolated nucleic acid molecule comprising anucleic acid sequence selected from the group consisting of SEQ IDNO:2n-1, wherein n is an integer between 1 and
 44. 21. The nucleic acidmolecule of claim 20, wherein the nucleic acid molecule is naturallyoccurring.
 22. A nucleic acid molecule, wherein the nucleic acidmolecule differs by a single nucleotide from a nucleic acid sequenceselected from the group consisting of SEQ ID NO: 2n-1, wherein n is aninteger between 1 and
 44. 23. An isolated nucleic acid molecule encodingthe mature form of a polypeptide having an amino acid sequence selectedfrom the group consisting of SEQ ID NO:2n, wherein n is an integerbetween 1 and
 44. 24. An isolated nucleic acid molecule comprising anucleic acid selected from the group consisting of 2n-1, wherein n is aninteger between 1 and
 44. 25. The nucleic acid molecule of claim 20,wherein said nucleic acid molecule hybridizes under stringent conditionsto the nucleotide sequence selected from the group consisting of SEQ IDNO:2n-1, wherein n is an integer between 1 and 44, or a complement ofsaid nucleotide sequence.
 26. A vector comprising the nucleic acidmolecule of claim
 20. 27. The vector of claim 26, further comprising apromoter operably linked to said nucleic acid molecule.
 28. A cellcomprising the vector of claim
 26. 29. An antibody thatimmunospecifically binds to the polypeptide of claim
 1. 30. The antibodyof claim 29, wherein the antibody is a monoclonal antibody.
 31. Theantibody of claim 29, wherein the antibody is a humanized antibody. 32.A method for determining the presence or amount of the nucleic acidmolecule of claim 20 in a sample, the method comprising: (a) providingsaid sample; (b) introducing said sample to a probe that binds to saidnucleic acid molecule; and (c) determining the presence or amount ofsaid probe bound to said nucleic acid molecule, thereby determining thepresence or amount of the nucleic acid molecule in said sample.
 33. Themethod of claim 32 wherein presence or amount of the nucleic acidmolecule is used as a marker for cell or tissue type
 34. The method ofclaim 33 wherein the cell or tissue type is cancerous.
 35. A method fordetermining the presence of or predisposition to a disease associatedwith altered levels of expression of the nucleic acid molecule of claim20 in a first mammalian subject, the method comprising: a) measuring thelevel of expression of the nucleic acid in a sample from the firstmammalian subject; and b) comparing the level of expression of saidnucleic acid in the sample of step (a) to the level of expression of thenucleic acid present in a control sample from a second mammalian subjectknown not to have or not be predisposed to, the disease; wherein analteration in the level of expression of the nucleic acid in the firstsubject as compared to the control sample indicates the presence of orpredisposition to the disease.
 36. A method of producing the polypeptideof claim 1, the method comprising culturing a cell under conditions thatlead to expression of the polypeptide, wherein said cell comprises avector comprising an isolated nucleic acid molecule comprising a nucleicacid sequence selected from the group consisting of SEQ ID NO:2n-1,wherein n is an integer between 1 and
 44. 37. The method of claim 36wherein the cell is a bacterial cell.
 38. The method of claim 36 whereinthe cell is an insect cell.
 39. The method of claim 36 wherein the cellis a yeast cell.
 40. The method of claim 36 wherein the cell is amammalian cell.
 41. A method of producing the polypeptide of claim 2,the method comprising culturing a cell under conditions that lead toexpression of the polypeptide, wherein said cell comprises a vectorcomprising an isolated nucleic acid molecule comprising a nucleic acidsequence selected from the group consisting of SEQ ID NO:2n-1, wherein nis an integer between 1 and
 44. 42. The method of claim 41 wherein thecell is a bacterial cell.
 43. The method of claim 41 wherein the cell isan insect cell.
 44. The method of claim 41 wherein the cell is a yeastcell.
 45. The method of claim 41 wherein the cell is a mammalian cell.